Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere's disease

Eur J Hum Genet. 2017 Feb;25(2):200-207. doi: 10.1038/ejhg.2016.154. Epub 2016 Nov 23.


Autosomal dominant (AD) familial Meniere's disease (FMD) is a rare disorder involving the inner ear defined by sensorineural hearing loss, tinnitus and episodic vertigo. Here, we have identified two novel and rare heterozygous variants in the SEMA3D and DPT genes segregating with the complete phenotype that have variable expressivity in two pedigrees with AD-FMD. A detailed characterization of the phenotype within each family illustrates the clinical heterogeneity in the onset and progression of the disease. We also showed the expression of both genes in the human cochlea and performed in silico analyses of these variants. Three-dimensional protein modelling showed changes in the structure of the protein indicating potential physical interactions. These results confirm a genetic heterogeneity in FMD with incomplete penetrance and variable expressivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chondroitin Sulfate Proteoglycans / chemistry
  • Chondroitin Sulfate Proteoglycans / genetics*
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Cochlea / metabolism
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Genes, Dominant
  • Genetic Heterogeneity*
  • Humans
  • Male
  • Meniere Disease / diagnosis
  • Meniere Disease / genetics*
  • Middle Aged
  • Molecular Dynamics Simulation
  • Pedigree
  • Penetrance*
  • Phenotype
  • Semaphorins / chemistry
  • Semaphorins / genetics*
  • Semaphorins / metabolism


  • Chondroitin Sulfate Proteoglycans
  • DPT protein, human
  • Extracellular Matrix Proteins
  • Sema3D protein, human
  • Semaphorins