Clinical characteristics.

Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity.

Pathogenic variants in MT-RNR1 can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset SNHL. Hearing loss associated with aminoglycoside ototoxicity is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount (even a single dose) of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin.

Pathogenic variants in MT-TS1 are usually associated with childhood onset of SNHL that is generally nonsyndromic – although the MT-TS1 substitution m.7445A>G has been found in some families who also have palmoplantar keratoderma (scaling, hyperkeratosis, and honeycomb appearance of the skin of the palms, soles, and heels).

Diagnosis/testing.

The diagnosis of mitochondrial nonsyndromic hearing loss and deafness is established in a proband with hearing loss and identification of a pathogenic variant in MT-RNR1 or MT-TS1, or one of the eight additional mitochondrial genes known to cause nonsyndromic hearing loss and deafness.

Management.

Treatment of manifestations: Appropriate rehabilitation (hearing aids, speech therapy, culturally appropriate language training, cochlear implantation, educational programs for the hearing impaired). Electric acoustic stimulation for individuals with mitochondrial hearing loss with residual hearing in the lower frequencies. Lotions and emollients for mild keratoderma; dermatology referral for severe keratoderma.

Prevention of primary manifestations: Avoidance of aminoglycosides.

Surveillance: Annual audiometric assessment to evaluate stability/progression of hearing loss. Annual physical exam for related clinical findings.

Agents/circumstances to avoid: Aminoglycosides and noise exposure, especially in those with normal hearing who have the m.1555A>G or m.1494C>T MT-RNR1 pathogenic variants.

Evaluation of relatives at risk: Molecular genetic testing of at-risk maternal relatives allows for early detection of those who have inherited the mtDNA pathogenic variant and would benefit from avoiding aminoglycosides and appropriate early support and management.

Genetic counseling.

Mitochondrial nonsyndromic hearing loss and deafness is caused by pathogenic variants in mitochondrial DNA (mtDNA) and is transmitted by maternal inheritance. The mother of a proband (usually) has the mtDNA pathogenic variant and may or may not have hearing loss. All offspring of females with a mtDNA pathogenic variant are at risk of inheriting the pathogenic variant. Offspring of males with a mtDNA pathogenic variant are not at risk of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk is possible if the mtDNA pathogenic variant in the family is known. Because of mitotic segregation, the mtDNA pathogenic variant load in amniocytes and chorionic villi is unlikely to correspond to that of other fetal or adult tissues. Furthermore, the presence of the mtDNA pathogenic variant does not predict the age of onset or severity of hearing loss.

Suggestive Findings

Mitochondrial nonsyndromic hearing loss and deafness should be suspected in a proband with the following:

• Moderate-to-profound hearing loss
  Hearing loss graded by level of severity:
  • Mild (26-40 dB)
  • Moderate (41-55 dB)
  • Moderately severe (56-70 dB)
  • Severe (71-90 dB)
  • Profound (90 dB)
  Hearing is assessed by a variety of methods; see Hereditary Hearing Loss and Deafness Overview.
• Mild-to-moderate high-frequency hearing loss
• No other systemic findings on history or physical examination
• A family history of hearing loss suggestive of maternal inheritance (i.e., no transmission through a male)
• Onset of hearing loss following administration of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin

Establishing the Diagnosis

The diagnosis of mitochondrial nonsyndromic hearing loss and deafness is established in a proband with the above suggestive findings and a pathogenic variant in one of the genes associated with mitochondrial nonsyndromic hearing loss and deafness identified by molecular genetic testing (see Table 1a, Table 1b).

Molecular genetic testing approaches can include targeted testing, a multigene panel, and complete mtDNA sequencing:

• Targeted testing. In individuals with hearing loss following aminoglycoside exposure, molecular testing for the pathogenic variants m.1555A>G and m.1494C>T in MT-RNR1 and m.7445A>C/T/G in MT-TS1 can be done first.
• A multigene panel that includes the mitochondrial genes listed in Table 1a and other genes of interest (see Table 1b and Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. (4) Some mitochondrial nonsyndromic deafness-causing pathogenic variants are heteroplasmic (i.e., both wild type and mutated mtDNA are present in a cell and/or tissue). When selecting a multigene panel, it is necessary to confirm that the test methods can identify heteroplasmic mitochondrial pathogenic variants.
  For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
• Complete mtDNA sequencing may be considered if use of targeted testing and/or a multigene panel did not identify a pathogenic variant, clinical suspicion remains high, and there is no evidence of paternal transmission. Massively parallel DNA sequencing-based techniques are useful for identifying heteroplasmic mitochondrial pathogenic variants.
  Note: This testing may be performed before a multigene panel in the case of a clear mitochondrial inheritance pattern.

Clinical Description

Phenotype Correlations by Gene

See Clinical Description.

Genotype-Phenotype Correlations

MT-TS1. The m.7445A>G pathogenic variant is associated in some families with palmoplantar keratoderma in addition to hearing loss. Individuals who have both the m.7444G>A and m.1555A>G (MT-RNR1) pathogenic variants [Pandya et al 2004] or the m.7443A>G pathogenic variant alone do not have skin findings.

Penetrance

MT-RNR1

• Most m.1555A>G pathogenic variants occur as homoplasmic changes; the penetrance of hearing loss is believed to be 100% in those with the pathogenic variant who receive aminoglycoside antibiotics (i.e., all individuals with this pathogenic variant will become deaf with any amount of aminoglycoside in a single dose) – although neonates who were unaffected following treatment with aminoglycosides have been reported [Ealy et al 2011, Göpel et al 2014]. However, aminoglycoside exposure may increase the lifetime risk for developing deafness.
• The penetrance for hearing loss in individuals with the m.1555A>G pathogenic variant who are not exposed to aminoglycosides varies widely (0%-65%) [Bykhovskaya et al 1998, Estivill et al 1998, Ding et al 2009, Lu et al 2010b]. Zhu et al [2014] reported that the heteroplasmy level of the m.1555A>G pathogenic variant correlated with hearing loss penetrance in five families with different heteroplasmy levels; penetrance in these families was 52%, 18.2%, 10%, 26.7%, and 44%.
• The averaged penetrance of eight Chinese families harboring the m.1494C>T pathogenic variant was 31.7% when aminoglycoside-induced deafness was included and 17.5% when it was excluded [Zhao et al 2004, Chen et al 2007].
• Variants m.961T>G and m.961_962delTinsC(n) have been associated with SNHL [Guaran et al 2013] but may be either benign or low-penetrance pathogenic.

Note: It has been suggested that penetrance for hearing loss is lower in some families from China [Young et al 2005, Dai et al 2006, Tang et al 2007].

MT-TS1. The pathogenic variants exist as both homoplasmic and heteroplasmic; therefore, the severity of hearing loss and age of onset vary depending on the mutational load in an individual.

Prevalence

The prevalence of mitochondrial nonsyndromic hearing loss and deafness has been well studied for MT-RNR1 and MT-TS1 in many populations.

In a prospective study in the Tianjin Province in China in which 58,000 newborns were screened with both audiologic and genetic methods, Zhang et al [2013] identified a pathogenic mtDNA variant in 1.8% of newborns; however, only one newborn was found to have hearing loss.

MT-RNR1. Hearing loss caused by MT-RNR1 pathogenic variant m.1555A>G has been observed worldwide (e.g., in the Arab-Israeli, Japanese, Mongolian, Zairean, Spanish, Chinese, Turkish, Balinese, Moroccan, Greek, Polish, Tunisian, and American populations) and is identified in 15% of all individuals with hearing loss and a history of aminoglycoside administration [Fischel-Ghodsian et al 1997].

The prevalence of the m.1555A>G pathogenic variant varies by population (see Table 2).

The prevalence of MT-RNR1 pathogenic variant m.1494C>T varies by population (see Table 3).

The prevalence of the m.961_962delTinsC(n) pathogenic variants in deaf probands, initially determined by screening of anonymized blood spots from newborns in the state of Texas, revealed a prevalence of approximately 1% [Tang et al 2002]. More recent literature has identified varying frequencies for the three changes in this region [Guaran et al 2013, Yelverton et al 2013, Zhang et al 2013].

MT-TS1. The prevalence of pathogenic variants is 0.8%-1.1% in deaf probands studied from the United States [Arnos et al 2003] and from Mongolia [Pandya et al 1999], and 0.68% in probands from China [Tang et al 2015]. A Japanese family with the m.7511T>C pathogenic variant has been reported [Li et al 2005].

The prevalence of pathogenic variant m.7444G>A was 0.86% in individuals with hearing loss from the United States [Yelverton et al 2013] and 0.4% in individuals with hearing loss of Polish ancestry [Rydzanicz et al 2011], but it was not identified among 513 Greek individuals [Kokotas et al 2010] or 701 Chinese individuals [Chen et al 2014].

The prevalence of m.7511T>C was 1.2% in Japanese individuals with maternally inherited hearing loss [Yano et al 2014], and 0.04% in Chinese individuals with hearing loss [Tang et al 2015].

Evaluations Following Initial Diagnosis

To establish the extent of hearing loss and needs in an individual diagnosed with mitochondrial nonsyndromic hearing loss and deafness, the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Complete auditory assessment (See Hereditary Hearing Loss and Deafness Overview.)
• Examination of the skin for evidence of keratoderma
• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Treatment includes the following:

• Appropriate rehabilitation including hearing aids, speech therapy, culturally appropriate language training, and evaluation for eligibility for cochlear implantation [Sinnathuray et al 2003]
• Electric acoustic stimulation (EAS) for individuals with mitochondrial hearing loss with residual hearing in the lower frequencies [Usami et al 2012a]
• Enrollment in educational programs appropriate for the hearing impaired
• For mild keratoderma, use of lotions and emollients; for severe keratoderma, dermatologic evaluation

Prevention of Primary Manifestations

MT-RNR1-related aminoglycoside-induced ototoxicity. Physicians can inquire about a family history of aminoglycoside-induced hearing loss prior to the administration of aminoglycosides, either systemically or locally (e.g., into the cochlea as treatment for Meniere's disease). In individuals with a family history of aminoglycoside-induced hearing loss, alternatives to aminoglycoside treatment should be considered when possible.

In the US, aminoglycoside use is most common in the neonatal intensive care unit; however, the therapeutic imperative of treatment with antibiotics in a neonatal intensive care unit setting does not always lend itself to pre-treatment screening by molecular genetic testing.

• Bitner-Glindzicz et al [2009] report a population frequency of 0.19% for the A to G change in a European cohort of children age seven to nine years who had the pathogenic variant but did not have hearing loss because they were not exposed to aminoglycosides; they make an argument for screening on demand to avoid a preventable cause of hearing loss.
• In a commentary by Boles & Friedlich [2010], the authors suggest a prospective study into the feasibility of screening for these mitochondrial pathogenic variants (especially in busy neonatal units) in order to identify a preventable form of hearing loss.
• In the Tianjin Province in China, screening of 58,000 newborns by audiometry and molecular genetic testing determined that 1.8% of newborns had a pathogenic mitochondrial DNA variant and only one newborn had hearing loss [Zhang et al 2013].

Surveillance

The following are appropriate:

• Annual audiometric assessment to evaluate stability or progression of hearing loss
• Annual examination by a physician to assess for related clinical findings (e.g., palmoplantar keratosis)

Agents/Circumstances to Avoid

Aminoglycosides and noise exposure should be avoided, particularly in individuals with normal hearing who have the m.1555A>G or m.1494C>T MT-RNR1 pathogenic variant.

Evaluation of Relatives at Risk

In a family in which the mtDNA pathogenic variant is known, prospective molecular genetic testing of at-risk maternal relatives allows early detection of those who have inherited the mtDNA pathogenic variant and would benefit from:

• Avoiding aminoglycosides to prevent onset of hearing loss
• Appropriate early support and management

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Use of aminoglycoside antibiotics during pregnancy in a mother who has the MT-RNR1 m.1555A>G or m.1494C>T pathogenic variants should be considered only in the absence of other treatment options, as these antibiotics exhibit incomplete placental transfer.

Of note, if the mother has the MT-RNR1 m.1555A>G or m.1494C>T pathogenic variant, she will pass it on to the fetus; hence, use of aminoglycosides should be avoided in the newborn.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Mode of Inheritance

Mitochondrial nonsyndromic hearing loss and deafness is caused by pathogenic variants in mitochondrial DNA (mtDNA) and is transmitted by maternal inheritance.

Risk to Family Members

Parents of a proband

• The father of a proband is not at risk of having the mtDNA pathogenic variant.
• The mother of a proband (usually) has the mtDNA pathogenic variant and may or may not have hearing loss.
• Up to 85% of individuals with mitochondrial nonsyndromic hearing loss have no known family history of hearing loss. The explanation for apparently simplex cases may be the absence of a comprehensive and/or reliable family history or, in rare cases, a de novo mtDNA pathogenic variant in the proband.

Sibs of a proband

• The risk to the sibs depends on the genetic load of the mitochondrial pathogenic variant in the mother (e.g., a mother heteroplasmic for a mtDNA pathogenic variant may transmit a low level of mutated mtDNA to her offspring, thus conferring a lower disease risk than a mother homoplasmic for a mtDNA pathogenic variant).
• If the mother has the mtDNA pathogenic variant, all sibs will inherit the variant; however, the risk of hearing loss depends on (a) the mutational load (see Penetrance) and (b) exposure to aminoglycosides.

Offspring of a proband

• All offspring of females with a mtDNA pathogenic variant are at risk of inheriting the pathogenic variant.
• Offspring of males with a mtDNA pathogenic variant are not at risk of inheriting the pathogenic variant.

Other family members. The risk to other family members depends on the genetic status of the proband's mother: if the mother of the proband has a mtDNA pathogenic variant, her sibs and mother are also at risk.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Many culturally deaf individuals view medical advances in hearing loss as a threat to the existence of their culture; it is important to acknowledge this point of view. The counseling session provides an opportunity to educate the individual regarding the etiology and natural history of the hearing loss and to discuss appropriate resources for services and information; such counseling is generally well received. Issues of prevention, cochlear implants, reproduction, and family planning should be dealt with in a culturally sensitive manner [Arnos & Oelrich 2002]. (See also Hereditary Hearing Loss and Deafness Overview.)

The following points are noteworthy:

• Communication with individuals who are members of the Deaf community and who sign requires the services of a skilled interpreter.
• Members of the Deaf community may view deafness as a distinguishing characteristic and not as a handicap, impairment, or medical condition requiring a "treatment" or "cure," or to be "prevented."
• Many deaf people are interested in obtaining information about the cause of their own deafness, including information on medical, educational, and social services, rather than information about prevention, reproduction, or family planning.
• The use of certain terms is preferred: probability or chance vs risk; deaf and hard-of-hearing vs hearing impaired. Terms such as "abnormal" should be avoided.

Family planning

• The optimal time for the determination of genetic status and discussion of prenatal testing availability is before pregnancy.
• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are deaf or have a family history of deafness.

Prenatal Testing

Once a mtDNA nonsyndromic hearing loss and deafness-causing variant has been identified in the mother, prenatal testing is possible; however, it is typically not performed.

If the mother is homoplasmic for a pathogenic variant, genetic testing is not needed to predict that the fetus inherited the variant (based on the maternally inherited pattern); therefore, the results of prenatal testing for mitochondrial nonsyndromic hearing loss and deafness do not provide additional information.

If the mtDNA pathogenic variant is identified in the fetal tissue sampled:

• The mtDNA mutational load in amniocytes and chorionic villi is unlikely to correspond to that of other fetal or adult tissues because of mitotic segregation.
• The presence of the mtDNA pathogenic variant does not predict the occurrence, age of onset, or severity of hearing loss.

If the mtDNA variant is not identified in the fetal tissue sampled, the pathogenic variant is likely present in fetal tissue not sampled.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.

Author History

Shin-ya Nishio, PhD (2017-present)
Arti Pandya, MD, MBA; Virginia Commonwealth University Health System (2004-2017)
Shin-ichi Usami, MD, PhD (2017-present)

Revision History

• 14 June 2018 (sw) Comprehensive update posted live
• 3 July 2014 (me) Comprehensive update posted live
• 21 April 2011 (me) Comprehensive update posted live
• 24 July 2007 (me) Comprehensive update posted live
• 22 October 2004 (me) Review posted live
• 13 August 2003 (ap) Original submission

Published Guidelines / Consensus Statements

• American College of Medical Genetics and Genomics. Guideline for the clinical evaluation and etiologic diagnosis of hearing loss (pdf). Available online. 2014. Accessed 5-25-22. [PubMed: 24651602]

Literature Cited

• Arnos KS, Oelrich MK. Genetic counseling for deafness. In: Keats BJB, Fay R, Popper A, eds. Genetics and Auditory Disorders. New York: Springer-Verlag; 2002:297-314.
• Arnos KS, Xia XJ, Norris G, Landa B. Relative frequencies of the mitochondrial A1555G and 961 del T mutations in the 12SrRNA gene in a large sample of deaf probands from the United States. Am J Hum Genet. 2003;73:S543.
• Ballana E, Morales E, Rabionet R, Montserrat B, Ventayol M, Bravo O, Gasparini P, Estivill X. Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment. Biochem Biophys Res Commun. 2006;341:950–7. [PubMed: 16458854]
• Bardien S, Human H, Harris T, Hefke G, Veikondis R, Schaaf HS, van der Merwe L, Greinwald JH, Fagan J, de Jong G. A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness. BMC Med Genet. 2009;10:2. [PMC free article: PMC2630920] [PubMed: 19144107]
• Bates DE. Aminoglycoside ototoxicity. Drugs Today (Barc). 2003;39:277–85. [PubMed: 12743643]
• Bitner-Glindzicz M, Pembrey M, Duncan A, Heron J, Ring SM, Hall A, Rahman S. Prevalence of mitochondrial 1555A-->G mutation in European children. N Engl J Med. 2009;360:640–2. [PubMed: 19196684]
• Boles RG, Friedlich P. Should patients be screened for 12SrRNA mutations before treatment with aminoglycosides? Mitochondrion. 2010;10:391–2. [PubMed: 20302974]
• Bravo O, Ballana E, Estivill X. Cochlear alterations in deaf and unaffected subjects carrying the deafness-associated A1555G mutation in the mitochondrial 12S rRNA gene. Biochem Biophys Res Commun. 2006;344:511–6. [PubMed: 16631122]
• Bykhovskaya Y, Shohat M, Ehrenman K, Johnson D, Hamon M, Cantor RM, Aouizerat B, Bu X, Rotter JI, Jaber L, Fischel-Ghodsian N. Evidence for complex nuclear inheritance in a pedigree with nonsyndromic deafness due to a homoplasmic mitochondrial mutation. Am J Med Genet. 1998;77:421–6. [PubMed: 9632174]
• Caria H, Matos T, Oliveira-Soares R, Santos AR, Galhardo I, Soares-Almeida L, Dias O, Andrea M, Correia C, Fialho G. A7445G mtDNA mutation present in a Portuguese family exhibiting hereditary deafness and palmoplantar keratoderma. J Eur Acad Dermatol Venereol. 2005;19:455–8. [PubMed: 15987292]
• Chen G, Wang X, Fu S. Prevalence of A1555G mitochondrial mutation in Chinese newborns and the correlation with neonatal hearing screening. Int J Pediatr Otorhinolaryngol. 2011;75:532–4. [PubMed: 21324532]
• Chen J, Yang L, Yang A, Zhu Y, Zhao J, Sun D, Tao Z, Tang X, Wang J, Wang X, Tsushima A, Lan J, Li W, Wu F, Yuan Q, Ji J, Feng J, Wu C, Liao Z, Li Z, Greinwald JH, Lu J, Guan MX. Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss is associated with the 12S rRNA C1494T mutation in three Han Chinese pedigrees. Gene. 2007;401:4–11. [PMC free article: PMC2014725] [PubMed: 17698299]
• Chen J, Yuan H, Lu J, Liu X, Wang G, Zhu Y, Cheng J, Wang X, Han B, Yang L, Yang S, Yang A, Sun Q, Kang D, Zhang X, Dai P, Zhai S, Han D, Young WY, Guan MX. Mutations at position 7445 in the precursor of mitochondrial tRNA(Ser(UCN)) gene in three maternal Chinese pedigrees with sensorineural hearing loss. Mitochondrion. 2008;8:285–92. [PubMed: 18639500]
• Chen K, Zong L, Liu M, Wang X, Zhou W, Zhan Y, Cao H, Dong C, Tang H, Jiang H. Developing regional genetic counseling for southern Chinese with nonsyndromic hearing impairment: a unique mutational spectrum. J Transl Med. 2014;12:64. [PMC free article: PMC3975227] [PubMed: 24612839]
• Dai P, Liu X, Han D, Qian Y, Huang D, et al. Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: implication for early detection and prevention of deafness. Biochem Biophys Res Commun. 2006;340:194–9. [PubMed: 16375862]
• del Castillo FJ, Villamar M, Moreno-Pelayo MA, Almela JJ, Morera C, Adiego I, Moreno F, del Castillo I. Maternally inherited non-syndromic hearing impairment in a Spanish family with the 7510T>C mutation in the mitochondrial tRNASer(UCN) gene. J Med Genet. 2002;39:e82. [PMC free article: PMC1757234] [PubMed: 12471220]
• Ding Y, Li Y, You J, Yang L, Chen B, Lu J, Guan MX. Mitochondrial tRNA(Glu) A14693G variant may modulate the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in a Han Chinese family. J Genet Genomics. 2009;36:241–50. [PubMed: 19376484]
• Ding Y, Xia BH, Liu Q, Li MY, Huang SX, Zhuo GC. Allele-specific PCR for detecting the deafness-associated mitochondrial 12S rRNA mutations. Gene. 2016;591:148–52. [PubMed: 27397648]
• Ealy M, Lynch KA, Meyer NC, Smith RJ. The prevalence of mitochondrial mutations associated with aminoglycoside-induced sensorineural hearing loss in an NICU population. Laryngoscope. 2011;121:1184–6. [PubMed: 21495045]
• Ensink RJ, Verhoeven K, Marres HA, Huygen PL, Padberg GW, ter Laak H, van Camp G, Willems PJ, Cremers CW. Early-onset sensorineural hearing loss and late-onset neurologic complaints caused by a mitochondrial mutation at position 7472. Arch Otolaryngol Head Neck Surg. 1998;124:886–91. [PubMed: 9708714]
• Estivill X, Govea N, Barceló E, Badenas C, Romero E, Moral L, Scozzri R, D'Urbano L, Zeviani M, Torroni A. Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides. Am J Hum Genet. 1998;62:27–35. [PMC free article: PMC1376822] [PubMed: 9490575]
• Fischel-Ghodsian N, Prezant TR, Chaltraw WE, Wendt KA, Nelson RA, Arnos KS, Falk RE. Mitochondrial gene mutation is a significant predisposing factor in aminoglycoside ototoxicity. Am J Otolaryngol. 1997;18:173–8. [PubMed: 9164619]
• Göpel W, Berkowski S, Preuss M, Ziegler A, Küster H, Felderhoff-Müser U, Gortner L, Mögel M, Härtel C, Herting E, et al. Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants. BMC Pediatr. 2014;14:210. [PMC free article: PMC4236616] [PubMed: 25155176]
• Gravina LP, Foncuberta ME, Estrada RC, Barreiro C, Chertkoff L. Carrier frequency of the 35delG and A1555G deafness mutations in the Argentinean population. Impact on the newborn hearing screening. Int J Pediatr Otorhinolaryngol. 2007;71:639–43. [PubMed: 17276518]
• Guan MX. Mitochondrial 12S rRNA mutations associated with aminoglycoside ototoxicity. Mitochondrion. 2011;11:237–45. [PubMed: 21047563]
• Guan MX. Molecular pathogenetic mechanism of maternally inherited deafness. Ann N Y Acad Sci. 2004;1011:259–71. [PubMed: 15126302]
• Guan MX, Enriquez JA, Fischel-Ghodsian N, Puranam RS, Lin CP, Maw MA, Attardi G. The deafness-associated mitochondrial DNA mutation at position 7445, which affects tRNASer(UCN) precursor processing, has long-range effects on NADH dehydrogenase subunit ND6 gene expression. Mol Cell Biol. 1998;18:5868–79. [PMC free article: PMC109173] [PubMed: 9742104]
• Guaran V, Astolfi L, Castiglione A, Simoni E, Olivetto E, Galasso M, Trevisi P, Busi M, Volinia S, Martini A. Association between idiopathic hearing loss and mitochondrial DNA mutations: a study on 169 hearing-impaired subjects. Int J Mol Med. 2013;32:785–94. [PMC free article: PMC3812239] [PubMed: 23969527]
• Hamasaki K, Rando RR. Specific binding of aminoglycosides to a human rRNA construct based on a DNA polymorphism which causes aminoglycoside-induced deafness. Biochemistry. 1997;36:12323–8. [PubMed: 9315872]
• Han B, Zong L, Li Q, Zhang Z, Wang D, Lan L, Zhang J, Zhao Y, Wang Q. Newborn genetic screening for high risk deafness-associated mutations with a new Tetra-primer ARMS PCR kit. Int J Pediatr Otorhinolaryngol. 2013;77:1440–5. [PubMed: 23815884]
• Hobbie SN, Akshay S, Kalapala SK, Bruell CM, Shcherbakov D, Böttger EC. Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity. Proc Natl Acad Sci U S A. 2008a;105:20888–93. [PMC free article: PMC2634874] [PubMed: 19104050]
• Hobbie SN, Bruell CM, Akshay S, Kalapala SK, Shcherbakov D, Böttger EC. Mitochondrial deafness alleles confer misreading of the genetic code. Proc Natl Acad Sci U S A. 2008b;105:3244–9. [PMC free article: PMC2265171] [PubMed: 18308926]
• Hutchin TP, Parker MJ, Young ID, Davis AC, Pulleyn LJ, Deeble J, Lench NJ, Markham AF, Mueller RF. A novel mutation in the mitochondrial tRNA(Ser(UCN)) gene in a family with non-syndromic sensorineural hearing impairment. J Med Genet. 2000;37:692–4. [PMC free article: PMC1734692] [PubMed: 10978361]
• Iwanicka-Pronicka K, Pollak A, Skórka A, Lechowicz U, Korniszewski L, Westfal P, Skarżyński H, Płoski R. Audio profiles in mitochondrial deafness m.1555A>G and m.3243A>G show distinct differences. Med Sci Monit. 2015;21:694–700. [PMC free article: PMC4360812] [PubMed: 25744662]
• Jacobs HT, Hutchin TP, Kappi T, Gillies G, Minkkinen K, Walker J, Thompson K, Rovio AT, Carella M, Melchionda S, Zelante L, Gasparini P, Pyykko I, Shah ZH, Zeviani M, Mueller RF. Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment. Eur J Hum Genet. 2005;13:26–33. [PubMed: 15292920]
• Ji YB, Han DY, Lan L, Wang DY, Zong L, Zhao FF, Liu Q, Benedict-Alderfer C, Zheng QY, Wang QJ. Molecular epidemiological analysis of mitochondrial DNA12SrRNA A1555G, GJB2, and SLC26A4 mutations in sporadic outpatients with nonsyndromic sensorineural hearing loss in China. Acta Otolaryngol. 2011;131:124–9. [PMC free article: PMC3528947] [PubMed: 21162657]
• Jiang Y, Huang S, Deng T, Wu L, Chen J, Kang D, Xu X, Li R, Han D, Dai P. Mutation spectrum of common deafness-causing genes in patients with non-syndromic deafness in the Xiamen area, China. PLoS One. 2015a;10:e0135088. [PMC free article: PMC4529078] [PubMed: 26252218]
• Jiang H, Liu Q, Chen L. Screening and analysis of mutation hot-spots in deafness-associated genes among adolescents with hearing loss. Mol Med Rep. 2015b;12:8179–84. [PubMed: 26499821]
• Jin L, Yang A, Zhu Y, Zhao J, Wang X, Yang L, Sun D, Tao Z, Tsushima A, Wu G, Xu L, Chen C, Yi B, Cai J, Tang X, Wang J, Li D, Yuan Q, Liao Z, Chen J, Li Z, Lu J, Guan MX. Mitochondrial tRNASer(UCN) gene is the hot spot for mutations associated with aminoglycoside-induced and non-syndromic hearing loss. Biochem Biophys Res Commun. 2007;361:133–9. [PubMed: 17659260]
• Jing W, Zongjie H, Denggang F, Na H, Bin Z, Aifen Z, Xijiang H, Cong Y, Yunping D, Ring HZ, Ring BZ. Mitochondrial mutations associated with aminoglycoside ototoxicity and hearing loss susceptibility identified by meta-analysis. J Med Genet. 2015;52:95–103. [PubMed: 25515069]
• Kameoka K, Isotani H, Tanaka K, Azukari K, Fujimura Y, Shiota Y, Sasaki E, Majima M, Furukawa K, Haginomori S, Kitaoka H, Ohsawa N. Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with diabetes. Biochem Biophys Res Commun. 1998;245:523–7. [PubMed: 9571188]
• Kokotas H, Grigoriadou M, Korres GS, Ferekidou E, Kandiloros D, Korres S, Petersen MB. Screening of a Greek deafness population for the A7445G mitochondrial DNA mutation. Mol Genet Metab. 2010;100:300–1. [PubMed: 20382059]
• Kokotas H, Grigoriadou M, Korres GS, Ferekidou E, Papadopoulou E, Neou P, Giannoulia-Karantana A, Kandiloros D, Korres S, Petersen MB. The A1555G mitochondrial DNA mutation in Greek patients with non-syndromic, sensorineural hearing loss. Biochem Biophys Res Commun. 2009;390:755–7. [PubMed: 19835846]
• King PJ, Ouyang X, Du L, Yan D, Angeli SI, Liu XZ. Etiologic diagnosis of nonsyndromic genetic hearing loss in adult vs pediatric populations. Otolaryngol Head Neck Surg. 2012;147:932–6. [PMC free article: PMC4511085] [PubMed: 22785241]
• Levinger L, Jacobs O, James M. In vitro 3'-end endonucleolytic processing defect in a human mitochondrial tRNA(Ser(UCN)) precursor with the U7445C substitution, which causes non-syndromic deafness. Nucleic Acids Res. 2001;29:4334–40. [PMC free article: PMC60182] [PubMed: 11691920]
• Lévêque M, Marlin S, Jonard L, Procaccio V, Reynier P, Amati-Bonneau P, Baulande S, Pierron D, Lacombe D, Duriez F, Francannet C, Mom T, Journel H, Catros H, Drouin-Garraud V, Obstoy MF, Dollfus H, Eliot MM, Faivre L, Duvillard C, Couderc R, Garabedian EN, Petit C, Feldmann D, Denoyelle F. Whole mitochondrial genome screening in maternally inherited non-syndromic hearing impairment using a microarray resequencing mitochondrial DNA chip. Eur J Hum Genet. 2007;15:1145–55. [PubMed: 17637808]
• Li Q, Yuan YY, Huang DL, Han DY, Dai P. Rapid screening for the mitochondrial DNA C1494T mutation in a deaf population in China using real-time quantitative PCR. Acta Otolaryngol. 2012;132:814–8. [PubMed: 22497215]
• Li R, Ishikawa K, Deng JH, Heman-Ackah S, Tamagawa Y, Yang L, Bai Y, Ichimura K, Guan MX. Maternally inherited nonsyndromic hearing loss is associated with the T7511C mutation in the mitochondrial tRNASerUCN gene in a Japanese family. Biochem Biophys Res Commun. 2005;328:32–7. [PubMed: 15670746]
• Li X, Fischel-Ghodsian N, Schwartz F, Yan Q, Friedman RA, Guan MX. Biochemical characterization of the mitochondrial tRNASer(UCN) T7511C mutation associated with nonsyndromic deafness. Nucleic Acids Res. 2004;32:867–77. [PMC free article: PMC373379] [PubMed: 14960712]
• Lightowlers RN, Taylor RW, Turnbull DM. Mutations causing mitochondrial disease: What is new and what challenges remain? Science. 2015;349:1494–9. [PubMed: 26404827]
• Liu H, Li R, Li W, Wang M, Ji J, Zheng J, Mao Z, Mo JQ, Jiang P, Lu J, Guan MX. Maternally inherited diabetes is associated with a homoplasmic T10003C mutation in the mitochondrial tRNA(Gly) gene. Mitochondrion. 2015;21:49–57. [PubMed: 25615420]
• Lu J, Li Z, Zhu Y, Yang A, Li R, Zheng J, Cai Q, Peng G, Zheng W, Tang X, Chen B, Chen J, Liao Z, Yang L, Li Y, You J, Ding Y, Yu H, Wang J, Sun D, Zhao J, Xue L, Wang J, Guan MX. Mitochondrial 12S rRNA variants in 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss. Mitochondrion. 2010a;10:380–90. [PMC free article: PMC2874659] [PubMed: 20100600]
• Lu J, Qian Y, Li Z, Yang A, Zhu Y, Li R, Yang L, Tang X, Chen B, Ding Y, Li Y, You J, Zheng J, Tao Z, Zhao F, Wang J, Sun D, Zhao J, Meng Y, Guan MX. Mitochondrial haplotypes may modulate the phenotypic manifestation of the deafness-associated 12S rRNA 1555A>G mutation. Mitochondrion. 2010b;10:69–81. [PMC free article: PMC2787746] [PubMed: 19818876]
• Ma Y, Xiao Y, Bai X, Zhang F, Zhang D, Xu X, Xu L, Wang H. GJB2, SLC26A4, and mitochondrial DNA12S rRNA hot-spots in 156 subjects with non-syndromic hearing loss in Tengzhou, China. Acta Otolaryngol. 2016a;136:800–5. [PubMed: 27066914]
• Ma D, Zhang J, Luo C, Lin Y, Ji X, Hu P, Xu Z. Genetic counseling for patients with nonsyndromic hearing impairment directed by gene analysis. Mol Med Rep. 2016b;13:1967–74. [PMC free article: PMC4769003] [PubMed: 26783197]
• Martin L, Toutain A, Guillen C, Haftek M, Machet MC, Toledano C, Arbeille B, Lorette G, Rötig A, Vaillant L. Inherited palmoplantar keratoderma and sensorineural deafness associated with A7445G point mutation in the mitochondrial genome. Br J Dermatol. 2000;143:876–83. [PubMed: 11069477]
• McFarland R, Taylor RW, Turnbull DM. A neurological perspective on mitochondrial disease. Lancet Neurol. 2010;9:829–40. [PubMed: 20650404]
• Mkaouar-Rebai E, Chamkha I, Mezghani N, Ben Ayed I, Fakhfakh F. Screening of mitochondrial mutations in Tunisian patients with mitochondrial disorders: an overview study. Mitochondrial DNA. 2013;24:163–78. [PubMed: 23301511]
• Mori K, Moteki H, Miyagawa M, Nishio SY, Usami S. Social health insurance-based simultaneous screening for 154 mutations in 19 deafness genes efficiently identified causative mutations in Japanese hearing loss patients. PLoS One. 2016;11:e0162230. [PMC free article: PMC5023092] [PubMed: 27627659]
• Nivoloni Kde A, da Silva-Costa SM, Pomílio MC, Pereira T, Lopes Kde C, de Moraes VC, Alexandrino F, de Oliveira CA, Sartorato EL. Newborn hearing screening and genetic testing in 8974 Brazilian neonates. Int J Pediatr Otorhinolaryngol. 2010;74:926–9. [PubMed: 20538352]
• Nye JS, Hayes EA, Amendola M, Vaughn D, Charrow J, McLone DG, Speer MC, Nance WE, Pandya A. Myelocystocele-cloacal exstrophy in a pedigree with a mitochondrial 12S rRNA mutation, aminoglycoside-induced deafness, pigmentary disturbances, and spinal anomalies. Teratology. 2000;61:165–71. [PubMed: 10661905]
• Pandya A, Xia X-J, Arnos KS, Norris V, Nance WE. The frequency of mitochondrial mutations in the 12SrRNA and tRNA ser (UCN) genes in deaf probands in a US repository. Abstract 102. Bethesda, MD: 5th Molecular Biology of Hearing & Deafness Meeting; 2004.
• Pandya A, Xia XJ, Erdenetungalag R, Amendola M, Landa B, Radnaabazar J, Dangaasuren B, Van Tuyle G, Nance WE. Heterogenous point mutations in the mitochondrial tRNA Ser(UCN) precursor coexisting with the A1555G mutation in deaf students from Mongolia. Am J Hum Genet. 1999;65:1803–6. [PMC free article: PMC1288397] [PubMed: 10577941]
• Reid FM, Vernham GA, Jacobs HT. A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness. Hum Mutat. 1994;3:243–7. [PubMed: 8019558]
• Rigoli L, Prisco F, Caruso RA, Iafusco D, Ursomanno G, Zuccarello D, Ingenito N, Rigoli M, Barberi I. Association of the T14709C mutation of mitochondrial DNA with maternally inherited diabetes mellitus and/or deafness in an Italian family. Diabet Med. 2001;18:334–6. [PubMed: 11437868]
• Rydzanicz M, Cywińska K, Wróbel M, Pollak A, Gawęcki W, Wojsyk-Banaszak I, Lechowicz U, Mueller-Malesińska M, Ołdak M, Płoski R, Skarżyński H, Szyfter K, Szyfter W. The contribution of the mitochondrial COI/tRNA(Ser(UCN)) gene mutations to non-syndromic and aminoglycoside-induced hearing loss in Polish patients. Mol Genet Metab. 2011;104:153–9. [PubMed: 21621438]
• Rydzanicz M, Wróbel M, Pollak A, Gawecki W, Brauze D, Kostrzewska-Poczekaj M, Wojsyk-Banaszak I, Lechowicz U, Mueller-Malesińska M, Ołdak M, Płoski R, Skarzyński H, Szyfter K. Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss. Biochem Biophys Res Commun. 2010;395:116–21. [PubMed: 20353758]
• Sevior KB, Hatamochi A, Stewart IA, Bykhovskaya Y, Allen-Powell DR, Fischel-Ghodsian N, Maw MA. Mitochondrial A7445G mutation in two pedigrees with palmoplantar keratoderma and deafness. Am J Med Genet. 1998;75:179–85. [PubMed: 9450881]
• Shen Z, Zheng J, Chen B, Peng G, Zhang T, Gong S, Zhu Y, Zhang C, Li R, Yang L, Zhou J, Cai T, Jin L, Lu J, Guan MX. Frequency and spectrum of mitochondrial 12S rRNA variants in 440 Han Chinese hearing impaired pediatric subjects from two otology clinics. J Transl Med. 2011;9:4. [PMC free article: PMC3029225] [PubMed: 21205314]
• Sinnathuray AR, Raut V, Awa A, Magee A, Toner JG. A review of cochlear implantation in mitochondrial sensorineural hearing loss. Otol Neurotol. 2003;24:418–26. [PubMed: 12806294]
• Sue CM, Tanji K, Hadjigeorgiou G, Andreu AL, Nishino I, Krishna S, Bruno C, Hirano M, Shanske S, Bonilla E, Fischel-Ghodsian N, DiMauro S, Friedman R. Maternally inherited hearing loss in a large kindred with a novel T7511C mutation in the mitochondrial DNA tRNA(Ser(UCN)) gene. Neurology. 1999;52:1905–8. [PubMed: 10371545]
• Suzuki S, Oka Y, Kadowaki T, Kanatsuka A, Kuzuya T, Kobayashi M, Sanke T, Seino Y, Nanjo K. Clinical features of diabetes mellitus with the mitochondrial DNA 3243 (A-G) mutation in Japanese: maternal inheritance and mitochondria-related complications. Diabetes Res Clin Pract. 2003;59:207–17. [PubMed: 12590018]
• Tang HY, Hutcheson E, Neill S, Drummond-Borg M, Speer M, Alford RL. Genetic susceptibility to aminoglycoside ototoxicity: how many are at risk? Genet Med. 2002;4:336–45. [PubMed: 12394346]
• Tang X, Li R, Zheng J, Cai Q, Zhang T, Gong S, Zheng W, He X, Zhu Y, Xue L, Yang A, Yang L, Lu J, Guan MX. Maternally inherited hearing loss is associated with the novel mitochondrial tRNA Ser(UCN) 7505T>C mutation in a Han Chinese family. Mol Genet Metab. 2010;100:57–64. [PubMed: 20153673]
• Tang X, Yang L, Zhu Y, Liao Z, Wang J, Qian Y, Tao Z, Hu L, Wu G, Lan J, Wang X, Ji J, Wu J, Ji Y, Feng J, Chen J, Li Z, Zhang X, Lu J, Guan MX. Very low penetrance of hearing loss in seven Han Chinese pedigrees carrying the deafness-associated 12S rRNA A1555G mutation. Gene. 2007;393:11–9. [PubMed: 17341440]
• Tang X, Zheng J, Ying Z, Cai Z, Gao Y, He Z, Yu H, Yao J, Yang Y, Wang H, Chen Y, Guan MX. Mitochondrial tRNA(Ser(UCN)) variants in 2651 Han Chinese subjects with hearing loss. Mitochondrion. 2015;23:17–24. [PubMed: 25968158]
• Tiranti V, Chariot P, Carella F, Toscano A, Soliveri P, Girlanda P, Carrara F, Fratta GM, Reid FM, Mariotti C, Zeviani M. Maternally inherited hearing loss, ataxia and myoclonus associated with a novel point mutation in mitochondrial tRNASer(UCN) gene. Hum Mol Genet. 1995;4:1421–7. [PubMed: 7581383]
• Uehara DT, Rincon D, Abreu-Silva RS, Auricchio MT, Tabith A, Kok F, Mingroni-Netto RC. Role of the mitochondrial mutations, m.827A>G and the novel m.7462C>T, in the origin of hearing loss. Genet Test Mol Biomarkers. 2010;14:611–6. [PubMed: 20722495]
• Usami S, Miyagawa M, Nishio SY, Moteki H, Takumi Y, Suzuki M, Kitano Y, Iwasaki S. Patients with CDH23 mutations and the 1555A>G mitochondrial mutation are good candidates for electric acoustic stimulation (EAS). Acta Otolaryngol. 2012a;132:377–84. [PMC free article: PMC3335139] [PubMed: 22443853]
• Usami S, Nishio SY, Nagano M, Abe S, Yamaguchi T, et al. Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study. PLoS One. 2012b;7:e31276. [PMC free article: PMC3286470] [PubMed: 22384008]
• Vandebona H, Mitchell P, Manwaring N, Griffiths K, Gopinath B, Wang JJ, Sue CM. Prevalence of mitochondrial 1555A-->G mutation in adults of European descent. N Engl J Med. 2009;360:642–4. [PubMed: 19196685]
• Verhoeven K, Ensink RJ, Tiranti V, Huygen PL, Johnson DF, Schatteman I, Van Laer L, Verstreken M, Van de Heyning P, Fischel-Ghodsian N, Zeviani M, Cremers CW, Willems PJ, Van Camp G. Hearing impairment and neurological dysfunction associated with a mutation in the mitochondrial tRNASer(UCN) gene. Eur J Hum Genet. 1999;7:45–51. [PubMed: 10094190]
• Wang Q, Li QZ, Han D, Zhao Y, Zhao L, Qian Y, Yuan H, Li R, Zhai S, Young WY, Guan MX. Clinical and molecular analysis of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss associated with the mitochondrial 12S rRNA C1494T mutation. Biochem Biophys Res Commun. 2006;340:583–8. [PubMed: 16380089]
• Wang M, Liu H, Zheng J, Chen B, Zhou M, Fan W, Wang H, Liang X, Zhou X, Eriani G, Jiang P, Guan MX. A deafness- and diabetes-associated tRNA mutation causes deficient pseudouridinylation at position 55 in tRNAGlu and mitochondrial dysfunction. J Biol Chem. 2016;291:21029–41. [PMC free article: PMC5076513] [PubMed: 27519417]
• Wei Q, Wang S, Yao J, Lu Y, Chen Z, Xing G, Cao X. Genetic mutations of GJB2 and mitochondrial 12S rRNA in nonsyndromic hearing loss in Jiangsu Province of China. J Transl Med. 2013 Jul 4;11:163. [PMC free article: PMC3706284] [PubMed: 23826813]
• Wu CC, Hung CC, Lin SY, Hsieh WS, Tsao PN, Lee CN, Su YN, Hsu CJ. Newborn genetic screening for hearing impairment: a preliminary study at a tertiary center. PLoS One. 2011;6:e22314. [PMC free article: PMC3139636] [PubMed: 21811586]
• Xu BC, Bian PP, Liu XW, Zhu YM, Yang XL, Ma JL, Chen XJ, Wang YL, Guo YF. Analysis of common deafness gene mutations in deaf people from unique ethnic groups in Gansu Province, China. Acta Otolaryngol. 2014;134:924–9. [PubMed: 24941117]
• Yan X, Wang X, Wang Z, Sun S, Chen G, He Y, Mo JQ, Li R, Jiang P, Lin Q, Sun M, Li W, Bai Y, Zhang J, Zhu Y, Lu J, Yan Q, Li H, Guan MX. Maternally transmitted late-onset non-syndromic deafness is associated with the novel heteroplasmic T12201C mutation in the mitochondrial tRNAHis gene. J Med Genet. 2011;48:682–90. [PubMed: 21931169]
• Yano T, Nishio SY, Usami S, et al. Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening. J Hum Genet. 2014;59:100–6. [PMC free article: PMC3970901] [PubMed: 24401907]
• Yelverton JC, Arnos K, Xia XJ, Nance WE, Pandya A, Dodson KM. The clinical and audiologic features of hearing loss due to mitochondrial mutations. Otolaryngol Head Neck Surg. 2013;148:1017–22. [PubMed: 23525847]
• Young WY, Zhao L, Qian Y, Wang Q, Li N, Greinwald JH Jr, Guan MX. Extremely low penetrance of hearing loss in four Chinese families with the mitochondrial 12S rRNA A1555G mutation. Biochem Biophys Res Commun. 2005;328:1244–51. [PubMed: 15708009]
• Yuan H, Chen J, Liu X, Cheng J, Wang X, Yang L, Yang S, Cao J, Kang D, Dai P, Zhai S, Han D, Young WY, Guan MX. Coexistence of mitochondrial 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations in two Han Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing loss. Biochem Biophys Res Commun. 2007;362:94–100. [PubMed: 17698030]
• Yuan H, Qian Y, Xu Y, Cao J, Bai L, Shen W, Ji F, Zhang X, Kang D, Mo JQ, Greinwald JH, Han D, Zhai S, Young WY, Guan MX. Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA(Ser(UCN)) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. Am J Med Genet A. 2005;138A:133–40. [PMC free article: PMC2759106] [PubMed: 16152638]
• Zhang Z, Ding W, Liu X, Xu B, Du W, Nan S, Guo Y. Auditory screening concurrent deafness predisposing genes screening in 10,043 neonates in Gansu province, China. Int J Pediatr Otorhinolaryngol. 2012;76:984–8. [PubMed: 22510577]
• Zhang J, Wang P, Han B, Ding Y, Pan L, Zou J, Liu H, Pang X, Liu E, Wang H, Liu H, Zhang X, Cheng X, Feng D, Li Q, Wang D, Zong L, Yi Y, Tian N, Mu F, Tian G, Chen Y, Liu G, Zhang F, Yi X, Yang L, Wang Q. Newborn hearing concurrent genetic screening for hearing impairment-a clinical practice in 58,397 neonates in Tianjin, China. Int J Pediatr Otorhinolaryngol. 2013;77:1929–35. [PubMed: 24100002]
• Zhao H, Li R, Wang Q, Yan Q, Deng JH, Han D, Bai Y, Young WY, Guan MX. Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family. Am J Hum Genet. 2004;74:139–52. [PMC free article: PMC1181901] [PubMed: 14681830]
• Zheng J, Ji Y, Guan MX. Mitochondrial tRNA mutations associated with deafness. Mitochondrion. 2012;12:406–13. [PubMed: 22538251]
• Zhu Y, Huang S, Kang D, Han M, Wang G, Yuan Y, Su Y, Yuan H, Zhai S, Dai P. Analysis of the heteroplasmy level and transmitted features in hearing-loss pedigrees with mitochondrial 12S rRNA A1555G mutation. BMC Genet. 2014;15:26. [PMC free article: PMC3933286] [PubMed: 24533451]
• Zhu Y, Li Q, Chen Z, Kun Y, Liu L, Liu X, Yuan H, Zhai S, Han D, Dai P. Mitochondrial haplotype and phenotype of 13 Chinese families may suggest multi-original evolution of mitochondrial C1494T mutation. Mitochondrion. 2009;9:418–28. [PubMed: 19682603]
• Zhu Y, Qian Y, Tang X, Wang J, Yang L, Liao Z, Li R, Ji J, Li Z, Chen J, Choo DI, Lu J, Guan MX. Aminoglycoside-induced and non-syndromic hearing loss is associated with the G7444A mutation in the mitochondrial COI/tRNASer(UCN) genes in two Chinese families. Biochem Biophys Res Commun. 2006;342:843–50. [PubMed: 16500624]