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01-01-2016 | Original Article

De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism

Authors: Linshan Shang, Lindsay B. Henderson, Megan T. Cho, Donald S. Petrey, Chin-To Fong, Katrina M. Haude, Natasha Shur, Julie Lundberg, Natalie Hauser, Jason Carmichael, Jeffrey Innis, Jane Schuette, Yvonne W. Wu, Shailesh Asaikar, Margaret Pearson, Leandra Folk, Kyle Retterer, Kristin G. Monaghan, Wendy K. Chung

Published in: Neurogenetics | Issue 1/2016

Abstract

Protein phosphatase 2A (PP2A) is a heterotrimeric protein serine/threonine phosphatase and is involved in a broad range of cellular processes. PPP2R5D is a regulatory B subunit of PP2A and plays an important role in regulating key neuronal and developmental regulation processes such as PI3K/AKT and glycogen synthase kinase 3 beta (GSK3β)-mediated cell growth, chromatin remodeling, and gene transcriptional regulation. Using whole-exome sequencing (WES), we identified four de novo variants in PPP2R5D in a total of seven unrelated individuals with intellectual disability (ID) and other shared clinical characteristics, including autism spectrum disorder, macrocephaly, hypotonia, seizures, and dysmorphic features. Among the four variants, two have been previously reported and two are novel. All four amino acids are highly conserved among the PP2A subunit family, and all change a negatively charged acidic glutamic acid (E) to a positively charged basic lysine (K) and are predicted to disrupt the PP2A subunit binding and impair the dephosphorylation capacity. Our data provides further support for PPP2R5D as a genetic cause of ID.

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Title: De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism
Authors: Linshan Shang
Lindsay B. Henderson
Megan T. Cho
Donald S. Petrey
Chin-To Fong
Katrina M. Haude
Natasha Shur
Julie Lundberg
Natalie Hauser
Jason Carmichael
Jeffrey Innis
Jane Schuette
Yvonne W. Wu
Shailesh Asaikar
Margaret Pearson
Leandra Folk
Kyle Retterer
Kristin G. Monaghan
Wendy K. Chung
Publication date: 01-01-2016
Publisher: Springer Berlin Heidelberg
Published in: Neurogenetics / Issue 1/2016
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-015-0466-9

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De novo missense variants in PPP2R5D are associated with intellectual disability, macrocephaly, hypotonia, and autism

Abstract

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Abstract

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