title: Macrothrombocytopenia and progressive deafness is due to a mutation in MYH9.
abstract: BACKGROUND
  In 1992, a family with hereditary macrothrombocytopenia and progressive sensorineural hearing impairment without renal dysfunction was described. Recently, mutations in MYH9, a nonmuscle myosin heavy chain, have been found in several forms of hereditary macrothrombocytopenia.
  
  
  OBJECTIVE
  The hereditary macrothrombocytopenia and hearing loss in the previously reported family is due to a mutation in MYH9 gene.
  
  
  METHODS
  Genomic DNA was extracted from the affected proband. Mutation screening of all MYH9 coding exons was carried out using denaturing high-performance liquid chromatography. Abnormal results were followed by direct sequencing of the exon and comparison of the sequence with the normal MYH9 sequence.
  
  
  RESULTS
  The results of denaturing high-performance liquid chromatography suggested a potential sequence alteration in exon 30 of MYH9. Direct sequence analysis of this exon in the affected individual identified a G to A single base pair transition at nucleotide 4270 altering codon 1424. This mutations leads to an amino acid change from aspartate (D) to asparagine (N) in the highly conserved coiled-coil domain.
  
  
  CONCLUSIONS
  A single base pair transition in MYH9, resulting in an amino acid substitution D1424N, is responsible for macrothrombocytopenia and hearing loss in the kindred under study. The presence of hearing impairment and the absence of renal symptoms, as reported in other families with the same mutation MYH9, further highlights the role of genetic background in expression and modification of the affected phenotype.
authors.affiliation: Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology-Head & Neck Surgery, University of California San Francisco, CA 94143, USA.
authors.forename: Anand N
authors.initials: AN
authors.lastname: Mhatre
authors.forename: Yuil
authors.initials: Y
authors.lastname: Kim
authors.forename: Hillary A
authors.initials: HA
authors.lastname: Brodie
authors.forename: Anil K
authors.initials: AK
authors.lastname: Lalwani
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics*; D006801:Humans; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D013921:Thrombocytopenia / Q000150:complications / Q000235:genetics*
chemical_list: D003062:Codon; D017931:DNA Primers; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains