Title |
De novo missense variants in PPP1CB are associated with intellectual disability and congenital heart disease
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Published in |
Human Genetics, September 2016
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DOI | 10.1007/s00439-016-1731-1 |
Pubmed ID | |
Authors |
Lijiang Ma, Yavuz Bayram, Heather M. McLaughlin, Megan T. Cho, Alyson Krokosky, Clesson E. Turner, Kristin Lindstrom, Caleb P. Bupp, Katey Mayberry, Weiyi Mu, Joann Bodurtha, Veronique Weinstein, Neda Zadeh, Wendy Alcaraz, Zöe Powis, Yunru Shao, Daryl A. Scott, Andrea M. Lewis, Janson J. White, Shalani N. Jhangiani, Elif Yilmaz Gulec, Seema R. Lalani, James R. Lupski, Kyle Retterer, Rhonda E. Schnur, Ingrid M. Wentzensen, Sherri Bale, Wendy K. Chung |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Scientists | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Doctoral Student | 6 | 16% |
Student > Bachelor | 6 | 16% |
Student > Ph. D. Student | 6 | 16% |
Researcher | 5 | 13% |
Student > Master | 4 | 11% |
Other | 3 | 8% |
Unknown | 8 | 21% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 8 | 21% |
Agricultural and Biological Sciences | 5 | 13% |
Medicine and Dentistry | 5 | 13% |
Computer Science | 3 | 8% |
Nursing and Health Professions | 3 | 8% |
Other | 3 | 8% |
Unknown | 11 | 29% |