Association of AHSG with alopecia and mental retardation (APMR) syndrome
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Alopecia with mental retardation syndrome (APMR) is a very rare autosomal recessive condition that is associated with total or partial absence of hair from the scalp and other parts of the body as well as variable intellectual disability. Here we present whole-exome sequencing results of a large consanguineous family segregating APMR syndrome with seven affected family members. Our study revealed a novel predicted pathogenic, homozygous missense mutation in the AHSG (OMIM 138680) gene (AHSG: NM_001622:exon7:c.950G>A:p.Arg317His). The variant is predicted to affect a region of the protein required for protein processing and disrupts a phosphorylation motif. In addition, the altered protein migrates with an aberrant size relative to healthy individuals. Consistent with the phenotype, AHSG maps within APMR linkage region 1 (APMR 1) as reported before, and falls within runs of homozygosity (ROH). Previous families with APMR syndrome have been studied through linkage analyses and the linkage resolution did not allow pointing out to a single gene candidate. Our study is the first report to identify a homozygous missense mutation for APMR syndrome through whole-exome sequencing.
KeywordsBone Morphogenetic Protein Signaling Phosphorylation Motif Exome Sequencing Project Exome Aggregation Consortium Advanced Sleep Phase Syndrome
We thank O. Dagan-Rosenfeld, A. Lipchik, A. Narasimha and H. Rost for many helpful discussions and input regarding the manuscript. M.R.S is supported by a grant from the Swiss National Science Foundation (SNSF). Work in the Snyder lab is supported by NIH Grants to M.P.S. (1P50HG00773501 and 8U54DK10255602). We thank the Stanford Center for Genomics and Personalized Medicine for their sequencing services.
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Conflict of interest
M. P. S. is a cofounder of Personalis and a member of the scientific advisory boards of Personalis and Genapsys.
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