A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14
- 24 February 2011
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 32 (6), 669-677
- https://doi.org/10.1002/humu.21488
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. Hum Mutat 32:1–9, 2011.This publication has 31 references indexed in Scilit:
- Myotonic dystrophy type I combined with X-linked dominant Charcot–Marie–Tooth neuropathyneurogenetics, 2010
- Variant CCG and GGC repeats within the CTG expansion dramatically modify mutational dynamics and likely contribute toward unusual symptoms in some myotonic dystrophy type 1 patientsHuman Molecular Genetics, 2010
- Diagnosis and new treatments in genetic neuropathiesJournal of Neurology, Neurosurgery & Psychiatry, 2009
- 165th ENMC International Workshop: Distal myopathies 6–8th February 2009 Naarden, The NetherlandsNeuromuscular Disorders, 2009
- Encephalopathic attacks in a family co-segregating myotonic dystrophy type 1, an intermediate Charcot-Marie-Tooth neuropathy and early hearing lossJournal of Neurology, Neurosurgery & Psychiatry, 2009
- Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal modelsneurogenetics, 2009
- Second family with hearing impairment linked to 19q13 and refined DFNA4 localisationEuropean Journal of Human Genetics, 2002
- Clinical and genetic aspects of distal myopathiesMuscle & Nerve, 2001
- Human Nonsyndromic Hereditary Deafness DFNA17 Is Due to a Mutation in Nonmuscle Myosin MYH9American Journal of Human Genetics, 2000
- Becker muscular dystrophy combined with x-linked Charcot-Marie-Tooth neuropathyMuscle & Nerve, 2000