PDF(Pubmed)
Abstract：
UNASSIGNED: Spinal muscular atrophy with lower extremity predominance 1 (SMALED1) and Charcot-Marie-Tooth diseasetype 2O (CMT2O) are two kinds of hereditary neuromuscular diseases caused by DYNC1H1 mutations. In this study, we reported two patients with SMALED1 caused by DYNC1H1 mutations. The genotype-phenotype correlations were further analyzed by systematically reviewing previous relevant publications.
UNASSIGNED: Two patients\' with SMALED1 and their parents\' clinical data were collected, and detailed clinical examinations were performed. WES was then applied, which was confirmed by Sanger sequencing. PubMed, Web of Science, CNKI, and Wanfang Data were searched, and all publications that met the inclusion criteria were carefully screened. Any individual patient without a detailed description of clinical phenotypes was excluded.
UNASSIGNED: The two patients manifested delayed motor milestones and muscle wasting of both lower extremities. The diagnosis was further confirmed as SMALED1. Genetic testing revealed heterozygous DYNC1H1 mutations c.1792C>T and c.790C>G; the latter is a novel dominant mutation. Genotype-phenotype analysis of DYNC1H1 variants and neuromuscular diseases revealed that mutations in the DYN1 region of DYNC1H1 protein were associated with a more severe phenotype, more complicated symptoms, and more CNS involvement than the DHC_N1 region.
UNASSIGNED: Our study potentially expanded the knowledge of the phenotypic and genetic spectrum of neuromuscular diseases caused by DYNC1H1 mutations. The genotype-phenotype correlation may reflect the pathogenesis underlying the dyneinopathy caused by DYNC1H1 mutations.
UNASSIGNED: Two patients\' with SMALED1 and their parents\' clinical data were collected, and detailed clinical examinations were performed. WES was then applied, which was confirmed by Sanger sequencing. PubMed, Web of Science, CNKI, and Wanfang Data were searched, and all publications that met the inclusion criteria were carefully screened. Any individual patient without a detailed description of clinical phenotypes was excluded.
UNASSIGNED: The two patients manifested delayed motor milestones and muscle wasting of both lower extremities. The diagnosis was further confirmed as SMALED1. Genetic testing revealed heterozygous DYNC1H1 mutations c.1792C>T and c.790C>G; the latter is a novel dominant mutation. Genotype-phenotype analysis of DYNC1H1 variants and neuromuscular diseases revealed that mutations in the DYN1 region of DYNC1H1 protein were associated with a more severe phenotype, more complicated symptoms, and more CNS involvement than the DHC_N1 region.
UNASSIGNED: Our study potentially expanded the knowledge of the phenotypic and genetic spectrum of neuromuscular diseases caused by DYNC1H1 mutations. The genotype-phenotype correlation may reflect the pathogenesis underlying the dyneinopathy caused by DYNC1H1 mutations.
摘要：
■以下肢为主的脊髓性肌萎缩症1（SMALED1）和Charcot-Marie-Tooth疾病型2O（CMT2O）是由DYNC1H1突变引起的两种遗传性神经肌肉疾病。在这项研究中,我们报道了2例由DYNC1H1突变引起的SMALED1患者.通过系统回顾以前的相关出版物，进一步分析了基因型-表型相关性。
■收集了两名SMALED1患者及其父母的临床数据，并进行了详细的临床检查.然后应用了WES，Sanger测序证实了这一点。PubMed,WebofScience,CNKI,搜索了万方数据，所有符合纳入标准的出版物均经过仔细筛选.排除任何没有临床表型详细描述的个体患者。
■两名患者表现为运动里程碑延迟和下肢肌肉萎缩。诊断进一步证实为SMALED1。遗传检测显示DYNC1H1杂合突变c.1792C>T和c.790C>G；后者是一种新的显性突变。DYNC1H1变异和神经肌肉疾病的基因型-表型分析显示，DYNC1H1蛋白的DYN1区域的突变与更严重的表型相关。更复杂的症状，与DHC_N1地区相比，中枢神经系统受累更多。
■我们的研究潜在地扩展了由DYNC1H1突变引起的神经肌肉疾病的表型和遗传谱的知识。基因型-表型相关性可能反映了由DYNC1H1突变引起的动力蛋白病的发病机理。
■收集了两名SMALED1患者及其父母的临床数据，并进行了详细的临床检查.然后应用了WES，Sanger测序证实了这一点。PubMed,WebofScience,CNKI,搜索了万方数据，所有符合纳入标准的出版物均经过仔细筛选.排除任何没有临床表型详细描述的个体患者。
■两名患者表现为运动里程碑延迟和下肢肌肉萎缩。诊断进一步证实为SMALED1。遗传检测显示DYNC1H1杂合突变c.1792C>T和c.790C>G；后者是一种新的显性突变。DYNC1H1变异和神经肌肉疾病的基因型-表型分析显示，DYNC1H1蛋白的DYN1区域的突变与更严重的表型相关。更复杂的症状，与DHC_N1地区相比，中枢神经系统受累更多。
■我们的研究潜在地扩展了由DYNC1H1突变引起的神经肌肉疾病的表型和遗传谱的知识。基因型-表型相关性可能反映了由DYNC1H1突变引起的动力蛋白病的发病机理。
