A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14 |
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Authors: | Choi Byung-Ok Kang Sung Hee 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 Kim Song Ja Züchner Stephan Chung Ki Wha |
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Affiliation: | Department of Neurology, Ewha Womans University School of Medicine, Seoul, Korea. |
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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. |
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Keywords: | hearing loss hoarseness genomewide scan MYH14 myopathy neuropathy |
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