title: A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14.
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.
authors.affiliation: Department of Neurology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Kang
authors.forename: Young Se
authors.initials: YS
authors.lastname: Hyun
authors.forename: Sumaria
authors.initials: S
authors.lastname: Kanwal
authors.forename: Sun Wha
authors.initials: SW
authors.lastname: Park
authors.forename: Heasoo
authors.initials: H
authors.lastname: Koo
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Kim
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Choi
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Yoo
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Kee Duk
authors.initials: KD
authors.lastname: Park
authors.forename: Kyoung-Gyu
authors.initials: KG
authors.lastname: Choi
authors.forename: Song Ja
authors.initials: SJ
authors.lastname: Kim
authors.forename: Stephan
authors.initials: S
authors.lastname: Züchner
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D006239:Haplotypes; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology; D006685:Hoarseness / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D024462:Myosin Type II / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea
chemical_list: D018995:Myosin Heavy Chains; D024462:Myosin Type II; C477830:MYH7b protein, human