Loss‐of‐Function Variant in PPP1R12A‐Related Urogenital and/or Brain Malformation Syndrome: Expanded Phenotype of Sex Reversal

Abstract

ABSTRACTDifferences of sex development (DSDs) are a heterogeneous group of congenital conditions in which chromosomal, gonadal, or anatomical sex does not match. The broad spectrum of phenotypes associated with DSDs requires accurate diagnosis, which influences the care and quality of life of affected patients. The decreasing costs of next‐generation sequencing (NGS) and international research collaborations in rare diseases have allowed the identification of new genes associated with DSDs. Recently, Hughes et al. in 2020 reported the association of loss‐of‐function (LoF) variants in PPP1R12A with morphological anomalies of the midline, including holoprosencephaly and urogenital malformations, also known as genitourinary and/or brain malformation syndrome (OMIM #618820). In this report, we describe a Mexican individual with hypertelorism, multiple skin hemangiomas, testicular atrophy, and sex reversal, in whom a c.1880delC frameshift variant in PPP1R12A was detected by exome sequencing. Segregation analysis confirmed it as a de novo variant through Sanger sequencing. The main objective of this report is to expand PPP1R12A‐related urogenital and/or brain malformation syndrome.