MYH9-related disease: five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations

Eur J Med Genet. 2013 Jan;56(1):7-12. doi: 10.1016/j.ejmg.2012.10.009. Epub 2012 Oct 30.

Abstract

MYH9-related disease (MYH9-RD) is a rare autosomal dominant syndromic disorder caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (myosin-9). MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy. The spectrum of mutations responsible for MYH9-RD is limited. We report five families, each with a novel MYH9 mutation. Two mutations, p.Val34Gly and p.Arg702Ser, affect the motor domain of myosin-9, whereas the other three, p.Met847_Glu853dup, p.Lys1048_Glu1054del, and p.Asp1447Tyr, hit the coiled-coil tail domain of the protein. The motor domain mutations were associated with more severe clinical phenotypes than those in the tail domain.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Base Sequence
  • Child
  • Child, Preschool
  • Exons
  • Female
  • Genes, Dominant
  • Genetic Association Studies
  • Humans
  • Male
  • Middle Aged
  • Models, Molecular
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Myosin Heavy Chains / chemistry
  • Myosin Heavy Chains / genetics*
  • Pedigree
  • Protein Conformation
  • Sequence Alignment
  • Syndrome
  • Thrombocytopenia / diagnosis
  • Thrombocytopenia / genetics*
  • Young Adult

Substances

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