ArticleAmerican journal of human genetics2020
Loss-of-Function Variants in PPP1R12A: From Isolated Sex Reversal to Holoprosencephaly Spectrum and Urogenital Malformations.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Epigenome-wide association analysis of prenatal organophosphate ester flame retardant exposure in maternal blood implicates maternal immune and neuronal epigenetic alterations.Environment international · 2026Article
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- A Novel PPP1R12A Splice-Site Variant Identified in a Female Fetus With Perineal Hamartoma.Prenatal diagnosis · 2026Article
- Integrating Polygenic Risk and Ocular Phenotyping Reveals an Axial-Length-Dominant Mechanism in High and Extreme High Myopia.Ophthalmology science · 2026Article
- Exome Sequencing in Prenatally Diagnosed Isolated Neural Tube Defects: A Subtype-Specific Analysis.Prenatal diagnosis · 2026Article
- A genetic model of congenital intestinal atresia implicates Mypt1 in epithelial organisation.Disease models & mechanisms · 2026Article
- Generation and characterization of a Cre-inducible MAP3K1 gain-of-function model.Disease models & mechanisms · 2026Article
- PPP1R12A Mutation Presenting With Congenital Jejunal Atresia and Short Stature: A Pediatric Endocrinology Case Report.Case reports in pediatrics · 2026Article
- Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review.Journal of applied genetics · 2025Article
- [46,XY disorder of sex development caused byZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
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- Modeling primary microcephaly with human brain organoids reveals fundamental roles of CIT kinase activity.The Journal of clinical investigation · 2024Article
- Functional analysis of a novel nonsense PPP1R12A variant in a Chinese family with infantile epilepsy.BMC medical genomics · 2024Article
- Article
- Phenotypic Features in a New 12q21 Deletion and Its Association With Cardiofaciocutaneous Syndrome.Cureus · 2024Article
- Clinical report and genetic analysis of a neonate with genitourinary and/or brain malformation syndrome caused by a non-coding sequence variant of PPP1R12A.Molecular genetics & genomic medicine · 2023Article
- Transcriptome Profiling Based at Different Time Points after Hatching Deepened Our Understanding on Larval Growth and Development ofMetabolites · 2023Article
- The Enigmatic Genetic Landscape of Hereditary Hearing Loss: A Multistep Diagnostic Strategy in the Italian Population.Biomedicines · 2023Article
- Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.Human molecular genetics · 2023Article
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Authors and funding
30 authors at 16 institutions in 3 countries.
Funding
Abstract
In two independent ongoing next-generation sequencing projects for individuals with holoprosencephaly and individuals with disorders of sex development, and through international research collaboration, we identified twelve individuals with de novo loss-of-function (LoF) variants in protein phosphatase 1, regulatory subunit 12a (PPP1R12A), an important developmental gene involved in cell migration, adhesion, and morphogenesis. This gene has not been previously reported in association with human disease, and it has intolerance to LoF as illustrated by a very low observed-to-expected ratio of LoF variants in gnomAD. Of the twelve individuals, midline brain malformations were found in five, urogenital anomalies in nine, and a combination of both phenotypes in two. Other congenital anomalies identified included omphalocele, jejunal, and ileal atresia with aberrant mesenteric blood supply, and syndactyly. Six individuals had stop gain variants, five had a deletion or duplication resulting in a frameshift, and one had a canonical splice acceptor site loss. Murine and human in situ hybridization and immunostaining revealed PPP1R12A expression in the prosencephalic neural folds and protein localization in the lower urinary tract at critical periods for forebrain division and urogenital development. Based on these clinical and molecular findings, we propose the association of PPP1R12A pathogenic variants with a congenital malformations syndrome affecting the embryogenesis of the brain and genitourinary systems and including disorders of sex development.
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