MedGen

Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to bacterial 16S ribosomal subunits. Aminoglycosides are associated with a number of adverse events, including nephrotoxicity and ototoxicity. The risk of aminoglycoside-induced ototoxicity is increased in patients who carry certain variants in the MT-RNR1 gene. MT-RNR1 is found in the mitochondrial genome and encodes the 12S ribosomal subunit. Some MT-RNR1 variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome. This ultimately results in hearing loss due to cell death in the cochlea. The Clinical Pharmacogenetics Implementation Consortium (CPIC) have published recommendations on aminoglycoside use in patients carrying MT-RNR1 variants in the journal Clinical Pharmacology and Therapeutics. These recommendations are also available on the CPIC and PharmGKB websites. [from PharmGKB]

Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to bacterial 16S ribosomal subunits. Aminoglycosides are associated with a number of adverse events, including nephrotoxicity and ototoxicity. The risk of aminoglycoside-induced ototoxicity is increased in patients who carry certain variants in the MT-RNR1 gene. MT-RNR1 is found in the mitochondrial genome and encodes the 12S ribosomal subunit. Some MT-RNR1 variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome. This ultimately results in hearing loss due to cell death in the cochlea. The Clinical Pharmacogenetics Implementation Consortium (CPIC) have published recommendations on aminoglycoside use in patients carrying MT-RNR1 variants in the journal Clinical Pharmacology and Therapeutics. These recommendations are also available on the CPIC and PharmGKB websites. [from PharmGKB]

Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to bacterial 16S ribosomal subunits. Aminoglycosides are associated with a number of adverse events, including nephrotoxicity and ototoxicity. The risk of aminoglycoside-induced ototoxicity is increased in patients who carry certain variants in the MT-RNR1 gene. MT-RNR1 is found in the mitochondrial genome and encodes the 12S ribosomal subunit. Some MT-RNR1 variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome. This ultimately results in hearing loss due to cell death in the cochlea. The Clinical Pharmacogenetics Implementation Consortium (CPIC) have published recommendations on aminoglycoside use in patients carrying MT-RNR1 variants in the journal Clinical Pharmacology and Therapeutics. These recommendations are also available on the CPIC and PharmGKB websites. [from PharmGKB]

Aminoglycosides are widely used antibiotics which inhibit protein synthesis in bacteria by binding to bacterial 16S ribosomal subunits. Aminoglycosides are associated with a number of adverse events, including nephrotoxicity and ototoxicity. The risk of aminoglycoside-induced ototoxicity is increased in patients who carry certain variants in the MT-RNR1 gene. MT-RNR1 is found in the mitochondrial genome and encodes the 12S ribosomal subunit. Some MT-RNR1 variants cause the 12S subunit to more closely resemble the bacterial 16S subunit, which can lead to aminoglycoside molecules binding to the ribosome. This ultimately results in hearing loss due to cell death in the cochlea. The Clinical Pharmacogenetics Implementation Consortium (CPIC) have published recommendations on aminoglycoside use in patients carrying MT-RNR1 variants in the journal Clinical Pharmacology and Therapeutics. These recommendations are also available on the CPIC and PharmGKB websites. [from PharmGKB]

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). [from GeneReviews]

Acute infantile liver failure resulting from TRMU mutation is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development (Zeharia et al., 2009). See also transient infantile mitochondrial myopathy (MMIT; 500009), which is a similar disorder. A more severe, permanent disorder with some overlapping features is associated with mitochondrial DNA depletion (251880). See ILFS1 (615438) for information on syndromic infantile liver failure. [from OMIM]

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). [from GeneReviews]