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 L Zuchner, Ki Wha Chung

Research output: Contribution to journalArticle

22 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
StatePublished - Jun 1 2011

Fingerprint

Hoarseness
Peripheral Nervous System Diseases
Muscular Diseases
Hearing Loss
Phenotype
Mutation
Muscle Weakness
Muscles
Genes
Distal Myopathies
Myosin Heavy Chains
Haplotypes
Atrophy
Single Nucleotide Polymorphism
Leg
Extremities
Hand
Chromosomes

Keywords

  • Genomewide scan
  • Hearing loss
  • Hoarseness
  • MYH14
  • Myopathy
  • Neuropathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14. / Choi, Byung Ok; Hee Kang, Sung; Hyun, Young Se; Kanwal, Sumaria; Park, Sun Wha; Koo, Heasoo; Kim, Sang Beom; Choi, Young Chul; Yoo, Jeong Hyun; Kim, Jong Won; Park, Kee Duk; Choi, Kyoung Gyu; Ja Kim, Song; Zuchner, Stephan L; Chung, Ki Wha.

In: Human Mutation, Vol. 32, No. 6, 01.06.2011, p. 669-677.

Research output: Contribution to journalArticle

Choi, BO, Hee Kang, S, Hyun, YS, Kanwal, S, Park, SW, Koo, H, Kim, SB, Choi, YC, Yoo, JH, Kim, JW, Park, KD, Choi, KG, Ja Kim, S, Zuchner, SL & Chung, KW 2011, 'A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14', Human Mutation, vol. 32, no. 6, pp. 669-677. https://doi.org/10.1002/humu.21488
Choi, Byung Ok ; Hee Kang, Sung ; Hyun, Young Se ; Kanwal, Sumaria ; Park, Sun Wha ; Koo, Heasoo ; Kim, Sang Beom ; Choi, Young Chul ; Yoo, Jeong Hyun ; Kim, Jong Won ; Park, Kee Duk ; Choi, Kyoung Gyu ; Ja Kim, Song ; Zuchner, Stephan L ; Chung, Ki Wha. / A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14. In: Human Mutation. 2011 ; Vol. 32, No. 6. pp. 669-677.
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AU - Kanwal, Sumaria

AU - Park, Sun Wha

AU - Koo, Heasoo

AU - Kim, Sang Beom

AU - Choi, Young Chul

AU - Yoo, Jeong Hyun

AU - Kim, Jong Won

AU - Park, Kee Duk

AU - Choi, Kyoung Gyu

AU - Ja Kim, Song

AU - Zuchner, Stephan L

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