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Identification of a novel MICU1 nonsense variant causes myopathy with extrapyramidal signs in an Iranian consanguineous family
Molecular and Cellular Pediatrics Pub Date : 2021-05-09 , DOI: 10.1186/s40348-021-00116-w
Fatemeh Bitarafan , Mehrnoosh Khodaeian , Elham Amjadi Sardehaei , Fatemeh Zahra Darvishi , Navid Almadani , Yalda Nilipour , Masoud Garshasbi

Ca2+ as a universal second messenger regulates basic biological functions including cell cycle, cell proliferation, cell differentiation, and cell death. Lack of the protein mitochondrial calcium uptake1 (MICU1), which has been regarded as a gatekeeper of Ca ions, leads to the abnormal mitochondrial Ca2+ handling, excessive production of reactive oxygen species (ROS), and increased cell death. Mutations in MICU1 gene causes a very rare neuromuscular disease, myopathy with extrapyramidal signs (MPXPS), due to primary alterations in mitochondrial calcium signaling which demonstrates the key role of mitochondrial Ca2+ uptake. To date, 13 variants have been reported in MICU1 gene in 44 patients presented with the vast spectrum of symptoms. Here, we report a 44-year-old Iranian patient presented with learning disability, muscle weakness, easy fatigability, reduced tendon reflexes, ataxia, gait disturbance, elevated hepatic transaminases, elevated serum creatine kinase (CK), and elevated lactate dehydrogenase (LDH). We identified a novel nonsense variant c.385C>T; p.(R129*) in MICU1 gene by whole exome sequencing (WES) and segregation analysis. Our finding along with previous studies provides more evidence on the clinical presentation of the disease caused by pathogenic mutations in MICU1. Finding more variants and expanding the spectrum of the disease increases the diagnostic rate of molecular testing in screening of this kind of diseases and in turn improves the quality of counseling for at risk couples and helps them to minimize the risks of having affected children.

中文翻译:

伊朗近亲家庭中新型MICU1废话变体的鉴定导致具有锥体束外征象的肌病

Ca2 +作为通用的第二信使调节着基本的生物学功能,包括细胞周期,细胞增殖,细胞分化和细胞死亡。蛋白质线粒体钙摄取1(MICU1)缺乏被认为是Ca离子的守门员,导致线粒体Ca2 +处理异常,活性氧(ROS)过量产生,并增加了细胞死亡。MICU1基因的突变会导致非常罕见的神经肌肉疾病,即具有锥体束外信号的肌病(MPXPS),这是由于线粒体钙信号传导的主要变化所致,这表明线粒体Ca2 +摄取的关键作用。迄今为止,已报道44例表现出广泛症状的患者的MICU1基因有13种变异。在这里,我们报道了一名44岁的伊朗患者,患有学习障碍,肌肉无力,易疲劳,腱反射减少,共济失调,步态紊乱,肝转氨酶升高,血清肌酸激酶(CK)升高和乳酸脱氢酶(LDH)升高。我们鉴定了一个新颖的废话变体c.385C> T;通过全外显子组测序(WES)和分离分析获得MICU1基因中的p。(R129 *)。我们的发现以及先前的研究为由MICU1中的致病性突变引起的疾病的临床表现提供了更多证据。寻找更多的变异体并扩大疾病的范围,可以提高筛查此类疾病的分子检测的诊断率,进而提高对高危夫妇的咨询质量,并帮助他们最大程度地降低患上患病儿童的风险。血清肌酸激酶(CK)升高,乳酸脱氢酶(LDH)升高。我们鉴定了一个新颖的废话变体c.385C> T;通过全外显子组测序(WES)和分离分析获得MICU1基因中的p。(R129 *)。我们的发现以及先前的研究为由MICU1中的致病性突变引起的疾病的临床表现提供了更多证据。寻找更多的变异体并扩大疾病的范围,可以提高筛查此类疾病的分子检测的诊断率,进而提高对高危夫妇的咨询质量,并帮助他们最大程度地降低患上患病儿童的风险。血清肌酸激酶(CK)升高,乳酸脱氢酶(LDH)升高。我们鉴定了一个新颖的废话变体c.385C> T;通过全外显子组测序(WES)和分离分析获得MICU1基因中的p。(R129 *)。我们的发现以及先前的研究为由MICU1中的致病性突变引起的疾病的临床表现提供了更多证据。寻找更多的变异体并扩大疾病的范围,可以提高筛查此类疾病的分子检测的诊断率,进而提高对高危夫妇的咨询质量,并帮助他们最大程度地降低患上患病儿童的风险。我们的发现以及先前的研究为由MICU1中的致病性突变引起的疾病的临床表现提供了更多证据。寻找更多的变异体并扩大疾病的范围,可以提高筛查此类疾病的分子检测的诊断率,进而提高对高危夫妇的咨询质量,并帮助他们最大程度地降低患上患病儿童的风险。我们的发现以及先前的研究为由MICU1中的致病性突变引起的疾病的临床表现提供了更多证据。寻找更多的变异体并扩大疾病的范围,可以提高筛查此类疾病的分子检测的诊断率,进而提高对高危夫妇的咨询质量,并帮助他们最大程度地降低患上患病儿童的风险。
更新日期:2021-05-10
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