Matching two independent cohorts validates DPH1 as a gene responsible for autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies

Hum Mutat. 2015 Oct;36(10):1015-9. doi: 10.1002/humu.22843. Epub 2015 Aug 17.


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.

Keywords: DPH1; Matchmaker Exchange; Sensenbrenner; intellectual disability; rare disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone and Bones / abnormalities*
  • Child, Preschool
  • Cohort Studies
  • Craniosynostoses / genetics*
  • Dwarfism / genetics*
  • Ectodermal Dysplasia / genetics*
  • Female
  • Humans
  • Information Dissemination
  • Intellectual Disability / genetics*
  • Male
  • Minor Histocompatibility Antigens
  • Mutation, Missense*
  • Pedigree
  • Tumor Suppressor Proteins / genetics*
  • Young Adult


  • DPH1 protein, human
  • Minor Histocompatibility Antigens
  • Tumor Suppressor Proteins

Supplementary concepts

  • Cranioectodermal Dysplasia