A Homozygous MYH1 Variant Underlies Autosomal Recessive Isolated Recurrent Rhabdomyolysis

IF 1.7 4区 生物学 Q3 GENETICS & HEREDITY American Journal of Medical Genetics Part A Pub Date : 2024-12-17 DOI:10.1002/ajmg.a.63952
Eyyup Uctepe, Hanifenur Mancılar, Fatma Nisa Esen, Gokcen Gundogdu Unverengil, Barbara Vona, Ahmet Yesilyurt
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Abstract

Rhabdomyolysis is a severe condition involving the breakdown of skeletal muscle fibers, leading to the release of muscle components into the bloodstream, which can lead to potential complications such as acute kidney injury and electrolyte imbalances. The etiology of rhabdomyolysis is multifactorial, encompassing traumatic, exertional, metabolic, infectious, toxic, and genetic causes. Genetic causes, including variants in LPIN1, RYR1, and CACNA1S, are increasingly recognized as significant contributors to recurrent rhabdomyolysis. MYH1 has recently been identified as a candidate gene for recurrent rhabdomyolysis with limited evidence originating from a single patient. In this report, we describe a 35-year-old male, born to consanguineous parents, who presented with recurrent rhabdomyolysis attacks, beginning at age 28, characterized by muscle pain, weakness, and episodes of acute kidney injury requiring dialysis. During attacks, the patient exhibited remarkably elevated markers of muscle breakdown and mildly elevated creatine kinase levels between episodes. A muscle biopsy revealed non-specific myopathic changes. Exome sequencing analysis was carried out and revealed a novel homozygous variant (NM_005963.4: c.1825G>A [p.Val609Met]) in MYH1 segregating in a manner compatible with an autosomal recessive pattern. In summary, this case provides confirmatory support for the role of pathogenic MYH1 variants in the pathogenesis of recurrent rhabdomyolysis and emphasizes the importance of comprehensive genetic testing in patients with unexplained recurrent episodes of muscle breakdown. Further cases are necessary to fully elucidate the genotypic and phenotypic spectrum of MYH1-related muscle disorders.

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纯合子MYH1变异是常染色体隐性分离的复发性横纹肌溶解的基础。
横纹肌溶解是一种严重的疾病,涉及骨骼肌纤维的分解,导致肌肉成分释放到血液中,这可能导致潜在的并发症,如急性肾损伤和电解质失衡。横纹肌溶解的病因是多因素的,包括创伤、运动、代谢、感染、毒性和遗传原因。遗传原因,包括LPIN1、RYR1和CACNA1S的变异,越来越被认为是复发性横纹肌溶解的重要因素。MYH1最近被确定为复发性横纹肌溶解的候选基因,来自单个患者的证据有限。在这个报告中,我们描述了一个35岁的男性,父母是近亲,他在28岁开始出现反复的横纹肌溶解发作,特征是肌肉疼痛,虚弱,急性肾损伤发作,需要透析。在发作期间,患者表现出显著升高的肌肉分解和轻度升高的肌酸激酶水平发作之间。肌肉活检显示非特异性肌病改变。外显子组测序分析显示,MYH1中存在一种新的纯合变异(NM_005963.4: c.1825G> a [p.Val609Met]),其分离方式与常染色体隐性模式相一致。总之,本病例为致病性MYH1变异在复发性横纹肌溶解发病机制中的作用提供了证实性支持,并强调了对不明原因的肌肉分解复发发作患者进行全面基因检测的重要性。需要进一步的病例来充分阐明myh1相关肌肉疾病的基因型和表型谱。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
432
审稿时长
2-4 weeks
期刊介绍: The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts: Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders. Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .
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