Matching Two Independent Cohorts Validates DPH1 as a Gene Responsible for Autosomal Recessive Intellectual Disability with Short Stature, Craniofacial, and Ectodermal Anomalies

被引：36

作者：

Loucks, Catrina M. ^{[1
]}

Parboosingh, Jillian S. ^{[1
,2
]}

Shaheen, Ranad ^{[3
]}

Bernier, Francois P. ^{[1
,2
]}

McLeod, D. Ross ^{[1
]}

Seidahmed, Mohammed Z. ^{[4
]}

Puffenberger, Erik G. ^{[5
]}

Ober, Carole ^{[6
,7
]}

Hegele, Robert A. ^{[8
]}

Boycott, Kym M. ^{[9
]}

Alkuraya, Fowzan S. ^{[3
,10
,11
]}

Innes, A. Micheil ^{[1
,2
]}

机构：

[1] Univ Calgary, Cumming Sch Med, Dept Med Genet, Calgary, AB, Canada

[2] Univ Calgary, Alberta Childrens Hosp, Res Inst Child & Maternal Hlth, Calgary, AB, Canada

[3] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia

[4] Secur Forces Hosp, Dept Pediat, Riyadh 12625, Saudi Arabia

[5] Clin Special Children, Strasburg, PA USA

[6] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[7] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA

[8] Univ Western Ontario, Dept Paediat, London, ON, Canada

[9] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada

[10] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh 11533, Saudi Arabia

[11] King Abdulaziz City Sci & Technol, Saudi Human Genome Program, Riyadh 11442, Saudi Arabia

来源：

HUMAN MUTATION | 2015年 / 36卷 / 10期

关键词：

DPH1; Sensenbrenner; intellectual disability; rare disorders; Matchmaker Exchange; DIPHTHERIA-TOXIN; DISEASE GENE; TRANSLATION; DISORDERS; PHENOTYPE; DISCOVERY; FIDELITY; TOOL;

D O I：

10.1002/humu.22843

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. (C) 2015 Wiley Periodicals, Inc.

引用

页码：1015 / 1019

页数：5