Macrothrombocytopenia and progressive deafness is due to a mutation in MYH9

Anand N. Mhatre, Yuil Kim, Hilary A Brodie, Anil K. Lalwani

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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. Hypothesis: 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 MYH9 mutation, further highlights the role of genetic background in expression and modification of the affected phenotype.

Original languageEnglish (US)
Pages (from-to)205-209
Number of pages5
JournalOtology and Neurotology
Issue number2
StatePublished - Mar 2003


  • Denaturing high-performance liquid chromatography
  • Hearing impairment
  • Macrothrombocytopenia
  • MYH9

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Neuroscience(all)


Dive into the research topics of 'Macrothrombocytopenia and progressive deafness is due to a mutation in MYH9'. Together they form a unique fingerprint.

Cite this