R705H mutation of MYH9 is associated with MYH9-related disease and not only with non-syndromic deafness DFNA17

Clin Genet. 2015 Jul;88(1):85-9. doi: 10.1111/cge.12438. Epub 2014 Jul 26.

Abstract

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disease caused by mutation of MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (NMMHC-IIA). MYH9-RD patients have macrothrombocytopenia and granulocyte inclusions (pathognomonic sign of the disease) containing wild-type and mutant NMMHC-IIA. During life they might develop sensorineural hearing loss, cataract, glomerulonephritis, and elevation of liver enzymes. One of the MYH9 mutations, p.R705H, was previously reported to be associated with DFNA17, an autosomal dominant non-syndromic sensorineural hearing loss without any other features associated. We identified the same mutation in two unrelated families, whose four affected individuals had not only hearing impairment but also thrombocytopenia, giant platelets, leukocyte inclusions, as well as mild to moderate elevation of some liver enzymes. Our data suggest that DFNA17 should not be a separate genetic entity but part of the wide phenotypic spectrum of MYH9-RD characterized by congenital hematological manifestations and variable penetrance and expressivity of the extra-hematological features.

Keywords: DFNA17 non-syndromic sensorineural hearing loss; MYH9-related disease; macrothrombocytopenia; p.R705H mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child, Preschool
  • Female
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Middle Aged
  • Molecular Motor Proteins / genetics*
  • Mutation, Missense*
  • Myosin Heavy Chains / genetics*
  • Pedigree
  • Phenotype
  • Thrombocytopenia / congenital*
  • Thrombocytopenia / diagnosis
  • Thrombocytopenia / genetics

Substances

  • MYH9 protein, human
  • Molecular Motor Proteins
  • Myosin Heavy Chains

Supplementary concepts

  • MYH9-Related Disorders