ESPEYB17 6. Differences/Disorders of Sex Development and Transgender Medicine Differences/Disorders of Sex Development: Genetics (3 abstracts)
6.9. Loss-of-function variants in PPP1R12A: From isolated sex reversal to holoprosencephaly spectrum and urogenital malformations
Hughes JJ , Alkhunaizi E , Kruszka P , Pyle LC , Grange DK , Berger SI , Payne KK , Masser-Frye D , Hu T , Christie MR , Clegg NJ , Everson JL , Martinez AF , Walsh LE , Bedoukian E , Jones MC , Harris CJ , Riedhammer KM , Choukair D , Fechner PY , Rutter MM , Hufnagel SB , Roifman M , Kletter GB , Delot E , Vilain E , Lipinski RJ , Vezina CM , Muenke M & Chitayat D
To read the full abstract: Am J Hum Genet. 2020, Jan 2; 106: 121-8. doi: https://www.cell.com/ajhg/pdf/S0002-9297(19)30468-9.pdf
Protein phosphatase 1, regulatory subunit 12a (PPP1R12A) is an important developmental factor involved in cell migration, adhesion, and morphogenesis. It is involved in the formation of myosin phosphatase and is regulated by phosphorylation.
This paper identifies mutations in the PPP1R12A gene in 12 individuals with holoprosencephaly and DSD, using next generation sequencing in two projects. The clinical manifestations of affected cases showed a broad spectrum with no clear genotype-phenotype correlation. Five had neurological phenotypes with midbrain malformations, nine had urogenital malformations, and two had both. The genital manifestations included a broad spectrum, from partial gonadal dysgenesis with micropenis, hypospadias, and ambiguous genitalia with Müllerian duct remnants, to complete gonadal dysgenesis in a 46,XY individual. In nine patients the karyotype was 46,XY and in three 46,XX.
Using next generation sequencing and in situ hybridization studies in mice and human embryonic tissues, this study adds an important piece of information to the knowledge on the early sequence of events resulting in normal genital development and the pathophysiology leading to a DSD, including complex syndromic forms.
Volume 17
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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