TY - JOUR
T1 - De novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea
AU - Xia, Fan
AU - Bainbridge, Matthew N.
AU - Tan, Tiong Yang
AU - Wangler, Michael F.
AU - Scheuerle, Angela E.
AU - Zackai, Elaine H.
AU - Harr, Margaret H.
AU - Sutton, V. Reid
AU - Nalam, Roopa L.
AU - Zhu, Wenmiao
AU - Nash, Margot
AU - Ryan, Monique M.
AU - Yaplito-Lee, Joy
AU - Hunter, Jill V.
AU - Deardorff, Matthew A.
AU - Penney, Samantha J.
AU - Beaudet, Arthur L.
AU - Plon, Sharon E.
AU - Boerwinkle, Eric A.
AU - Lupski, James R.
AU - Eng, Christine M.
AU - Muzny, Donna M.
AU - Yang, Yaping
AU - Gibbs, Richard A.
N1 - Funding Information:
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.
PY - 2014/5/1
Y1 - 2014/5/1
N2 - 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. Further, many molecular diagnoses are guided by recent gene-disease association discoveries. Hence, there is a critical interplay between clinical testing and research leading to gene-disease association discovery. Here, we describe four probands, all of whom presented with hypotonia, intellectual disability, global developmental delay, and mildly dysmorphic facial features. Three of the four also had sleep apnea. Each was a simplex case without a remarkable family history. Using WES, we identified AHDC1 de novo truncating mutations that most likely cause this genetic syndrome.
AB - 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. Further, many molecular diagnoses are guided by recent gene-disease association discoveries. Hence, there is a critical interplay between clinical testing and research leading to gene-disease association discovery. Here, we describe four probands, all of whom presented with hypotonia, intellectual disability, global developmental delay, and mildly dysmorphic facial features. Three of the four also had sleep apnea. Each was a simplex case without a remarkable family history. Using WES, we identified AHDC1 de novo truncating mutations that most likely cause this genetic syndrome.
UR - http://www.scopus.com/inward/record.url?scp=84899806077&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899806077&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2014.04.006
DO - 10.1016/j.ajhg.2014.04.006
M3 - Article
C2 - 24791903
AN - SCOPUS:84899806077
SN - 0002-9297
VL - 94
SP - 784
EP - 789
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -