title: Matching two independent cohorts validates DPH1 as a gene responsible for autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Catrina M
authors.initials: CM
authors.lastname: Loucks
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jillian S
authors.initials: JS
authors.lastname: Parboosingh
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyhadh, 11211, Saudi Arabia.
authors.forename: Ranad
authors.initials: R
authors.lastname: Shaheen
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Francois P
authors.initials: FP
authors.lastname: Bernier
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: D Ross
authors.initials: DR
authors.lastname: McLeod
authors.affiliation: Department of Pediatrics, Security Forces Hospital, Riyadh, 12625, Saudi Arabia.
authors.forename: Mohammed Z
authors.initials: MZ
authors.lastname: Seidahmed
authors.affiliation: Clinic for Special Children, Strasburg, Pennsylvania.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
authors.affiliation: Department of Human Genetics, and Department of Obstetrics and Gynecology, The University of Chicago, Chicago, Illinois.
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.affiliation: Department of Paediatrics, University of Western Ontario, London, Ontario, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyhadh, 11211, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, 11533, Saudi Arabia.|Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, 11442, Saudi Arabia.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: A Micheil
authors.initials: AM
authors.lastname: Innes
mesh_terms: D000293:Adolescent; D001842:Bone and Bones / Q000002:abnormalities*; D002675:Child, Preschool; D015331:Cohort Studies; D003398:Craniosynostoses / Q000235:genetics*; D004392:Dwarfism / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D006801:Humans; D033181:Information Dissemination; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D015778:Minor Histocompatibility Antigens; D020125:Mutation, Missense; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C121987:DPH1 protein, human; D015778:Minor Histocompatibility Antigens; D025521:Tumor Suppressor Proteins
keywords: DPH1; Matchmaker Exchange; Sensenbrenner; intellectual disability; rare disorders