Journal article

De Novo Truncating Mutations in AHDC1 in Individuals with Syndromic Expressive Language Delay, Hypotonia, and Sleep Apnea

Fan Xia, Matthew N Bainbridge, Tiong Yang Tan, Michael F Wangler, Angela E Scheuerle, Elaine H Zackai, Margaret H Harr, V Reid Sutton, Roopa L Nalam, Wenmiao Zhu, Margot Nash, Monique M Ryan, Joy Yaplito-Lee, Jill V Hunter, Matthew A Deardorff, Samantha J Penney, Arthur L Beaudet, Sharon E Plon, Eric A Boerwinkle, James R Lupski Show all

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2014

Abstract

Clinical whole-exome sequencing (WES) for identification of mutations leading to Mendelian disease has been offered to the medical community since 2011. Clinically undiagnosed neurological disorders are the most frequent basis for test referral, and currently, approximately 25% of such cases are diagnosed at the molecular level. To date, there are approximately 4,000 "known" disease-associated loci, and many are associated with striking dysmorphic features, making genotype-phenotype correlations relatively straightforward. A significant fraction of cases, however, lack characteristic dysmorphism or clinical pathognomonic traits and are dependent upon molecular tests for definitive diagnoses...

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Grants

Awarded by NIH


Awarded by National Institute of Neurological Disorders and Stroke


Awarded by National Health and Medical Research Council of Australia


Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

We thank the families and clinical staff at all locations for participation in this study. This work was supported in part by NIH grants to R.A.G. (NHGRI 5 U54 HG003273), J.R.L. (NHGRI RO1NS058529 and U54HG006542), and S.E.P. (NHGRI 5 U01 HG006485). M.W. received funding from the National Institute of Neurological Disorders and Stroke (NS076547) and the Simons Foundation. T.Y.T. is partially supported by the National Health and Medical Research Council of Australia (fellowship 607431). Baylor College of Medicine performs genetic testing as a service for a fee. M.N.B. is a founder of Codified Genomics, and J.R.L. is a consultant for Athena Diagnostics, 23andMe, and Ion Torrent Systems Inc. and holds multiple US and European patents for DNA diagnostics.