De novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea.

TitleDe novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea.
Publication TypeJournal Article
Year of Publication2014
AuthorsXia, F, Bainbridge, MN, Tan, TYang, Wangler, MF, Scheuerle, AE, Zackai, EH, Harr, MH, V Sutton, R, Nalam, RL, Zhu, W, Nash, M, Ryan, MM, Yaplito-Lee, J, Hunter, JV, Deardorff, MA, Penney, SJ, Beaudet, AL, Plon, SE, Boerwinkle, E, Lupski, JR, Eng, CM, Muzny, DM, Yang, Y, Gibbs, RA
JournalAm J Hum Genet
Volume94
Issue5
Pagination784-9
Date Published2014 May 1
ISSN1537-6605
KeywordsChild, Child, Preschool, DNA-Binding Proteins, Exome, Female, Humans, Infant, Intellectual Disability, Language Development Disorders, Male, Muscle Hypotonia, Mutation, Sleep Apnea Syndromes, Syndrome
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. 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.

DOI10.1016/j.ajhg.2014.04.006
Alternate JournalAm. J. Hum. Genet.
PubMed ID24791903
PubMed Central IDPMC4067559
Grant ListK08 NS076547 / NS / NINDS NIH HHS / United States
5U01 HG006485 / HG / NHGRI NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
R01NS058529 / NS / NINDS NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U01 HG006485 / HG / NHGRI NIH HHS / United States
NS076547 / NS / NINDS NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States
5 U54 HG003273 / HG / NHGRI NIH HHS / United States