PDF(Pubmed)
Abstract：
UNASSIGNED: The etiology and pathogenesis of idiopathic dystonia remain obscure. Recent studies revealed that compound heterozygous mutations in collagen type VI alpha-3 gene COL6A3 may cause recessive isolated dystonia (DYT)-27. However, whether COL6A3 mutations are associated with Chinese patients with isolated dystonia is not yet reported.
UNASSIGNED: In this study, 45 Chinese patients with isolated cervical dystonia were recruited, and their blood DNA samples were subjected to whole-exome sequencing. The potential causal variants of COL6A3 were identified based on the criteria of the American College of Medical Genetics and Genomics and by prediction software.
UNASSIGNED: Among 45 isolated cervical dystonia patients, 18 patients (10 female patients and eight male patients) were found to have seven potential causal variants in the COL6A3 gene. Among these variants, a compound heterozygous mutation was found in one patient. One allele had a c.1264G>A mutation in exon 4 that resulted in an amino acid substitution of methionine for valine at codon 422 (p.Val422Met) and the other a c.8965+9G>A mutation involving a splicing change in exon 40. In addition, other five missense variants, including c.958G>A (p.Ala320Thr), c.1478T>C (p.Val493Ala), c.1597C>T (p.Arg533Cys), c.1762G>A (p.Asp588Asn), and c.4912G>A (p.Ala1638Thr), were identified as well.
UNASSIGNED: We identified a novel deleterious compound heterozygous mutation as well as five missense variants in the COL6A3 gene of Chinese patients with cervical dystonia. These findings may expand the spectrum of the COL6A3 genotype in isolated dystonia.
UNASSIGNED: In this study, 45 Chinese patients with isolated cervical dystonia were recruited, and their blood DNA samples were subjected to whole-exome sequencing. The potential causal variants of COL6A3 were identified based on the criteria of the American College of Medical Genetics and Genomics and by prediction software.
UNASSIGNED: Among 45 isolated cervical dystonia patients, 18 patients (10 female patients and eight male patients) were found to have seven potential causal variants in the COL6A3 gene. Among these variants, a compound heterozygous mutation was found in one patient. One allele had a c.1264G>A mutation in exon 4 that resulted in an amino acid substitution of methionine for valine at codon 422 (p.Val422Met) and the other a c.8965+9G>A mutation involving a splicing change in exon 40. In addition, other five missense variants, including c.958G>A (p.Ala320Thr), c.1478T>C (p.Val493Ala), c.1597C>T (p.Arg533Cys), c.1762G>A (p.Asp588Asn), and c.4912G>A (p.Ala1638Thr), were identified as well.
UNASSIGNED: We identified a novel deleterious compound heterozygous mutation as well as five missense variants in the COL6A3 gene of Chinese patients with cervical dystonia. These findings may expand the spectrum of the COL6A3 genotype in isolated dystonia.
摘要：
■特发性肌张力障碍的病因和发病机制仍不清楚。最近的研究表明，VI型胶原蛋白α-3基因COL6A3中的复合杂合突变可能导致隐性孤立性肌张力障碍（DYT）-27。然而,COL6A3突变是否与中国孤立性肌张力障碍患者相关,目前尚无报道.
■在这项研究中，招募45例中国孤立性宫颈肌张力障碍患者，和他们的血液DNA样本进行全外显子组测序。根据美国医学遗传学和基因组学学院的标准并通过预测软件鉴定了COL6A3的潜在因果变异。
■在45例孤立的宫颈肌张力障碍患者中，发现18名患者（10名女性患者和8名男性患者）在COL6A3基因中具有7种潜在的因果变异。在这些变体中，在一名患者中发现了复合杂合突变。一个等位基因在外显子4中具有c.1264G>A突变，该突变导致在密码子422处蛋氨酸被氨基酸取代为缬氨酸（p。Val422Met）和另一个c.89659G>A突变，涉及外显子40的剪接变化。此外,其他五个错觉变体，包括c.958G>A（p。Ala320Thr),c.1478T>C（p。Val493Ala),c.1597C>T（p。Arg533Cys)，c.1762G>A（p。Asp588Asn),和c.4912G>A（p。Ala1638Thr),也被确认了。
■我们在中国宫颈肌张力障碍患者的COL6A3基因中发现了一个新的有害复合杂合突变和五个错义变异。这些发现可能会扩大孤立的肌张力障碍中COL6A3基因型的范围。
■在这项研究中，招募45例中国孤立性宫颈肌张力障碍患者，和他们的血液DNA样本进行全外显子组测序。根据美国医学遗传学和基因组学学院的标准并通过预测软件鉴定了COL6A3的潜在因果变异。
■在45例孤立的宫颈肌张力障碍患者中，发现18名患者（10名女性患者和8名男性患者）在COL6A3基因中具有7种潜在的因果变异。在这些变体中，在一名患者中发现了复合杂合突变。一个等位基因在外显子4中具有c.1264G>A突变，该突变导致在密码子422处蛋氨酸被氨基酸取代为缬氨酸（p。Val422Met）和另一个c.89659G>A突变，涉及外显子40的剪接变化。此外,其他五个错觉变体，包括c.958G>A（p。Ala320Thr),c.1478T>C（p。Val493Ala),c.1597C>T（p。Arg533Cys)，c.1762G>A（p。Asp588Asn),和c.4912G>A（p。Ala1638Thr),也被确认了。
■我们在中国宫颈肌张力障碍患者的COL6A3基因中发现了一个新的有害复合杂合突变和五个错义变异。这些发现可能会扩大孤立的肌张力障碍中COL6A3基因型的范围。
