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Hypospadias 2, X-linked(HYSP2)

MedGen UID:
437064
•Concept ID:
C2677879
•
Disease or Syndrome
Synonym: HYSP2
 
Gene (location): MAMLD1 (Xq28)
 
Monarch Initiative: MONDO:0010423
OMIM®: 300758

Clinical features

From HPO
Penoscrotal hypospadias
MedGen UID:
105291
•Concept ID:
C0452147
•
Congenital Abnormality
A severe form of hypospadias in which the urethral opening is located at the junction of the penis and scrotum.
See: Feature record | Search on this feature

Recent clinical studies

Etiology

The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35.
Zanchetta ME, Napolitano LMR, Maddalo D, Meroni G
Biochim Biophys Acta Mol Cell Res 2017 Oct;1864(10):1844-1854. Epub 2017 Jul 29 doi: 10.1016/j.bbamcr.2017.07.014. PMID: 28760657
Genitourinary anomalies of pediatric FG syndrome.
Smith JF, Wayment RO, Cartwright PC, Snow BW, Opitz JM
J Urol 2007 Aug;178(2):656-9. Epub 2007 Jun 15 doi: 10.1016/j.juro.2007.04.007. PMID: 17574621
MID1 mutation screening in a large cohort of Opitz G/BBB syndrome patients: twenty-nine novel mutations identified.
Ferrentino R, Bassi MT, Chitayat D, Tabolacci E, Meroni G
Hum Mutat 2007 Feb;28(2):206-7. doi: 10.1002/humu.9480. PMID: 17221865
Isolation and characterisation of the chick orthologue of the Opitz syndrome gene, Mid1, supports a conserved role in vertebrate development.
Richman JM, Fu KK, Cox LL, Sibbons JP, Cox TC
Int J Dev Biol 2002;46(4):441-8. PMID: 12141430
Molecular basis of androgen insensitivity.
Brinkmann A, Jenster G, Ris-Stalpers C, van der Korput H, Brüggenwirth H, Boehmer A, Trapman J
Steroids 1996 Apr;61(4):172-5. doi: 10.1016/0039-128x(96)00008-6. PMID: 8732995

Diagnosis

Opitz syndrome: improving clinical interpretation of intronic variants in MID1 gene.
Micale L, Russo F, Mascaro M, Morlino S, Nardella G, Fusco C, Bisceglia L, Meroni G, Castori M
Pediatr Res 2023 Apr;93(5):1208-1215. Epub 2022 Aug 11 doi: 10.1038/s41390-022-02237-y. PMID: 35953512
SPECC1L Mutations Are Not Common in Sporadic Cases of Opitz G/BBB Syndrome.
Migliore C, Vendramin A, McKee S, Prontera P, Faravelli F, Sachdev R, Dias P, Mascaro M, Licastro D, Meroni G
Genes (Basel) 2022 Jan 28;13(2) doi: 10.3390/genes13020252. PMID: 35205294Free PMC Article
An X-linked syndrome with severe neurodevelopmental delay, hydrocephalus, and early lethality caused by a missense variation in the OTUD5 gene.
Tripolszki K, Sasaki E, Hotakainen R, Kassim AH, Pereira C, Rolfs A, Bauer P, Reardon W, Bertoli-Avella AM
Clin Genet 2021 Feb;99(2):303-308. Epub 2020 Nov 9 doi: 10.1111/cge.13873. PMID: 33131077
Onset Manifestations of Spinal and Bulbar Muscular Atrophy (Kennedy's Disease).
Finsterer J, Soraru G
J Mol Neurosci 2016 Mar;58(3):321-9. Epub 2015 Oct 19 doi: 10.1007/s12031-015-0663-x. PMID: 26482145
A novel mutation in MID1 in a patient with X-linked Opitz G/BBB syndrome.
Ji X, Xing Y, Xu Y, Liu Y, Chen Y, Tao J, Xiao B
Gene 2014 Mar 1;537(1):140-2. Epub 2013 Dec 26 doi: 10.1016/j.gene.2013.12.018. PMID: 24374473

Therapy

Androgen resistance associated with a qualitative abnormality of the androgen receptor and responsive to high dose androgen therapy.
Grino PB, Isidro-Gutierrez RF, Griffin JE, Wilson JD
J Clin Endocrinol Metab 1989 Mar;68(3):578-84. doi: 10.1210/jcem-68-3-578. PMID: 2918059

Prognosis

Opitz syndrome: improving clinical interpretation of intronic variants in MID1 gene.
Micale L, Russo F, Mascaro M, Morlino S, Nardella G, Fusco C, Bisceglia L, Meroni G, Castori M
Pediatr Res 2023 Apr;93(5):1208-1215. Epub 2022 Aug 11 doi: 10.1038/s41390-022-02237-y. PMID: 35953512
Prenatal diagnosis of maternally inherited X-linked Opitz G/BBB syndrome by chromosomal microarray in a fetus with complex congenital heart disease.
Cheng YK, Huang J, Law KM, Chan YM, Leung TY, Choy KW
Clin Chim Acta 2014 Sep 25;436:140-2. Epub 2014 May 23 doi: 10.1016/j.cca.2014.05.006. PMID: 24863803
Genitourinary anomalies of pediatric FG syndrome.
Smith JF, Wayment RO, Cartwright PC, Snow BW, Opitz JM
J Urol 2007 Aug;178(2):656-9. Epub 2007 Jun 15 doi: 10.1016/j.juro.2007.04.007. PMID: 17574621
ARX mutations in X-linked lissencephaly with abnormal genitalia.
Uyanik G, Aigner L, Martin P, Gross C, Neumann D, Marschner-Schäfer H, Hehr U, Winkler J
Neurology 2003 Jul 22;61(2):232-5. doi: 10.1212/01.wnl.0000079371.19562.ba. PMID: 12874405
Androgen resistance associated with a qualitative abnormality of the androgen receptor and responsive to high dose androgen therapy.
Grino PB, Isidro-Gutierrez RF, Griffin JE, Wilson JD
J Clin Endocrinol Metab 1989 Mar;68(3):578-84. doi: 10.1210/jcem-68-3-578. PMID: 2918059

Clinical prediction guides

SPECC1L Mutations Are Not Common in Sporadic Cases of Opitz G/BBB Syndrome.
Migliore C, Vendramin A, McKee S, Prontera P, Faravelli F, Sachdev R, Dias P, Mascaro M, Licastro D, Meroni G
Genes (Basel) 2022 Jan 28;13(2) doi: 10.3390/genes13020252. PMID: 35205294Free PMC Article
The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35.
Zanchetta ME, Napolitano LMR, Maddalo D, Meroni G
Biochim Biophys Acta Mol Cell Res 2017 Oct;1864(10):1844-1854. Epub 2017 Jul 29 doi: 10.1016/j.bbamcr.2017.07.014. PMID: 28760657
Structural and functional observations of the P151L MID1 mutation reveal alpha4 plays a significant role in X-linked Opitz Syndrome.
Wright KM, Du H, Massiah MA
FEBS J 2017 Jul;284(14):2183-2193. Epub 2017 Jun 14 doi: 10.1111/febs.14121. PMID: 28548391
XLOS-observed mutations of MID1 Bbox1 domain cause domain unfolding.
Wright KM, Wu K, Babatunde O, Du H, Massiah MA
PLoS One 2014;9(9):e107537. Epub 2014 Sep 12 doi: 10.1371/journal.pone.0107537. PMID: 25216264Free PMC Article
MID1 catalyzes the ubiquitination of protein phosphatase 2A and mutations within its Bbox1 domain disrupt polyubiquitination of alpha4 but not of PP2Ac.
Du H, Wu K, Didoronkute A, Levy MV, Todi N, Shchelokova A, Massiah MA
PLoS One 2014;9(9):e107428. Epub 2014 Sep 10 doi: 10.1371/journal.pone.0107428. PMID: 25207814Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • MeSH
      Related Medical Subject Headings
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed
    • PubMed (OMIM)
      Related literature resources in PubMed

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