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

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...

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Published in:Human mutation 2011-06, Vol.32 (6), p.669-677
Main Authors: 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, Züchner, Stephan, Chung, Ki Wha
Format: Article
Language:English
Subjects:
Adolescent
Adult
Amino Acid Sequence
Female
Genetic Association Studies
Genetic Linkage
genomewide scan
Haplotypes
hearing loss
Hearing Loss - genetics
Hearing Loss - pathology
hoarseness
Hoarseness - genetics
Hoarseness - pathology
Humans
Male
Middle Aged
Molecular Sequence Data
Muscular Diseases - genetics
Muscular Diseases - pathology
Mutation
MYH14
myopathy
Myosin Heavy Chains - genetics
Myosin Type II - genetics
neuropathy
Peripheral Nervous System Diseases - genetics
Peripheral Nervous System Diseases - pathology
Polymorphism, Single Nucleotide
Republic of Korea
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Summary: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. Hum Mutat 32:1–9, 2011. © 2011 Wiley‐Liss, Inc.
ISSN:1059-7794
1098-1004
1098-1004
DOI:10.1002/humu.21488