A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14

Byung Ok Choi, Sung Hee Kang, Young Se Hyun, Sumaria Kanwal, Sun Wha Park, Heasoo Koo, Sang Beom Kim, Young Chul Choi, Jeong Hyun Yoo, Jong Won Kim, Kee Duk Park, Kyoung Gyu Choi, Song Ja Kim, Stephan Züchner, Ki Wha Chung

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Both peripheral neuropathy and distal myopathy are well-established inherited neuromuscular disorders characterized by progressive weakness and atrophy of the distal limb muscles. A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss was diagnosed in a large autosomal dominant Korean family. A high density single nucleotide polymorphism (SNP)-based linkage study mapped the underlying gene to a region on chromosome 19q13.3. The maximum multipoint LOD score was 3.794. Sequencing of 34 positional candidate genes in the segregating haplotype revealed a novel c.2822G>T (p.Arg941Leu) mutation in the gene MYH14, which encodes the nonmuscle myosin heavy chain 14. Clinically we observed a sequential pattern of the onset of muscle weakness starting from the anterior to the posterior leg muscle compartments followed by involvement of intrinsic hand and proximal muscles. The hearing loss and hoarseness followed the onset of distal muscle weakness. Histopathologic and electrodiagnostic studies revealed both chronic neuropathic and myopathic features in the affected patients. Although mutations in MYH14 have been shown to cause nonsyndromic autosomal dominant hearing loss (DFNA4), the peripheral neuropathy, myopathy, and hoarseness have not been associated with MYH14. Therefore, we suggest that the identified mutation in MYH14 significantly expands the phenotypic spectrum of this gene.

Original languageEnglish
Pages (from-to)669-677
Number of pages9
JournalHuman mutation
Volume32
Issue number6
DOIs
Publication statusPublished - 2011 Jun

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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