A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14.
A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14.
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DOI：
10.1002/humu.21488
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发表时间：
2011-06
期刊：
影响因子：
3.9
通讯作者：
Chung, Ki Wha
中科院分区：
文献类型：
--
作者：
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;Zuechner, Stephan;Chung, Ki Wha
周围神经病和远端肌病都是公认的遗传性神经肌肉疾病，其特征是四肢远端肌肉的进行性无力和萎缩。在一个常染色体显性遗传的韩国大家族中诊断出一种复杂的表型，包括周围神经病、肌病、声音嘶哑和听力损失。一项基于SNP的高密度连锁研究将潜在基因定位到染色体19q13.3上的一个区域。最大多点LOD评分为3.794分。对分离单倍型中的34个位置候选基因进行测序，发现编码非肌肉肌球蛋白重链14的基因MYH14存在一种新的c.2822G>；T(p.Arg941Leu)突变。临床上，我们观察到了肌肉无力的顺序模式，从小腿前至后部肌肉间隔开始，然后累及手部和近端肌肉。听力损失和声音嘶哑是在远端肌肉无力开始后出现的。组织病理学和电诊断研究显示，在受影响的患者中既有慢性神经病理性特征，也有肌病特征。虽然MYH14基因突变已被证明可导致非综合征型常染色体显性遗传性听力损失(DFNA4)，但周围神经病、肌病和声音嘶哑与MYH14无关。因此，我们认为MYH14基因的突变显著扩大了该基因的表型谱。
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 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. While 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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