Title | De novo missense variants in PPP1CB are associated with intellectual disability and congenital heart disease. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Ma, L, Bayram, Y, McLaughlin, HM, Cho, MT, Krokosky, A, Turner, CE, Lindstrom, K, Bupp, CP, Mayberry, K, Mu, W, Bodurtha, J, Weinstein, V, Zadeh, N, Alcaraz, W, Powis, Z, Shao, Y, Scott, DA, Lewis, AM, White, JJ, Jhangiani, SN, Gulec, EYilmaz, Lalani, SR, Lupski, JR, Retterer, K, Schnur, RE, Wentzensen, IM, Bale, S, Chung, WK |
Journal | Hum Genet |
Volume | 135 |
Issue | 12 |
Pagination | 1399-1409 |
Date Published | 2016 12 |
ISSN | 1432-1203 |
Keywords | Adolescent, Adult, Child, Child, Preschool, Exome, Female, Genetic Association Studies, Genetic Predisposition to Disease, Heart Defects, Congenital, Humans, Intellectual Disability, Male, Mutation, Missense, Phosphorylation, Protein Phosphatase 1 |
Abstract | Intellectual disabilities are genetically heterogeneous and can be associated with congenital anomalies. Using whole-exome sequencing (WES), we identified five different de novo missense variants in the protein phosphatase-1 catalytic subunit beta (PPP1CB) gene in eight unrelated individuals who share an overlapping phenotype of dysmorphic features, macrocephaly, developmental delay or intellectual disability (ID), congenital heart disease, short stature, and skeletal and connective tissue abnormalities. Protein phosphatase-1 (PP1) is a serine/threonine-specific protein phosphatase involved in the dephosphorylation of a variety of proteins. The PPP1CB gene encodes a PP1 subunit that regulates the level of protein phosphorylation. All five altered amino acids we observed are highly conserved among the PP1 subunit family, and all are predicted to disrupt PP1 subunit binding and impair dephosphorylation. Our data suggest that our heterozygous de novo PPP1CB pathogenic variants are associated with syndromic intellectual disability. |
DOI | 10.1007/s00439-016-1731-1 |
Alternate Journal | Hum. Genet. |
PubMed ID | 27681385 |
PubMed Central ID | PMC5663278 |
Grant List | U54 HG006542 / HG / NHGRI NIH HHS / United States R01 GM030518 / GM / NIGMS NIH HHS / United States UM1 HG006542 / HG / NHGRI NIH HHS / United States R37 GM030518 / GM / NIGMS NIH HHS / United States R01 NS058529 / NS / NINDS NIH HHS / United States |