Premium
Matching Two Independent Cohorts Validates DPH1 as a Gene Responsible for Autosomal Recessive Intellectual Disability with Short Stature, Craniofacial, and Ectodermal Anomalies
Author(s) -
Loucks Catrina M.,
Parboosingh Jillian S.,
Shaheen Ranad,
Bernier Francois P.,
McLeod D. Ross,
Seidahmed Mohammed Z.,
Puffenberger Erik G.,
Ober Carole,
Hegele Robert A.,
Boycott Kym M.,
Alkuraya Fowzan S.,
Innes A. Micheil
Publication year - 2015
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22843
Subject(s) - biology , short stature , genetics , craniofacial , intellectual disability , gene , endocrinology
Recently, Alazami et al. (2015) identified 33 putative candidate disease genes for neurogenetic disorders. One such gene was DPH1 , in which a homozygous missense mutation was associated with a 3C syndrome‐like phenotype in four patients from a single extended family. Here, we report a second homozygous missense variant in DPH1 , seen in four members of a founder population, and associated with a phenotype initially reminiscent of Sensenbrenner syndrome. This postpublication “match” validates DPH1 as a gene underlying syndromic intellectual disability with short stature and craniofacial and ectodermal anomalies, reminiscent of, but distinct from, 3C and Sensenbrenner syndromes. This validation took several years after the independent discoveries due to the absence of effective methods for sharing both candidate phenotype and genotype data between investigators. Sharing of data via Web‐based anonymous data exchange servers will play an increasingly important role toward more efficient identification of the molecular basis for rare Mendelian disorders.