Peat Rachel A, Baker Naomi L, Jones Kristi J, North Kathryn N, Lamandé Shireen R
The Neurogenetics Research Unit, Children's Hospital, Westmead, Sydney, Australia.
Neuromuscul Disord. 2007 Jul;17(7):547-57. doi: 10.1016/j.nmd.2007.03.017. Epub 2007 May 29.
Collagen VI mutations cause mild Bethlem myopathy and severe, progressive Ullrich congenital muscular dystrophy (UCMD). We identified a novel homozygous COL6A1 premature termination mutation in a UCMD patient that causes nonsense-mediated mRNA decay. Collagen VI microfibrils cannot be detected in muscle or fibroblasts. The parents are heterozygous carriers of the mutation and their fibroblasts produce reduced amounts of collagen VI. The molecular findings in the parents are analogous to those reported for a heterozygous COL6A1 premature termination mutation that causes Bethlem myopathy. However, the parents of our UCMD proband are clinically normal. The proband's brother, also a carrier, has clinical features consistent with a mild collagen VI phenotype. Following a request for prenatal diagnosis in a subsequent pregnancy we found the fetus was a heterozygous carrier indicating that it would not be affected with severe UCMD. COL6A1 premature termination mutations exhibit variable penetrance necessitating a cautious approach to genetic counselling.
胶原蛋白VI突变可导致轻度的贝思伦肌病和严重的进行性乌尔里希先天性肌营养不良症（UCMD）。我们在一名UCMD患者中鉴定出一种新的纯合COL6A1过早终止突变，该突变导致无义介导的mRNA降解。在肌肉或成纤维细胞中无法检测到胶原蛋白VI微原纤维。父母是该突变的杂合携带者，他们的成纤维细胞产生的胶原蛋白VI量减少。父母的分子学发现与报道的导致贝思伦肌病的杂合COL6A1过早终止突变的情况类似。然而，我们UCMD先证者的父母临床正常。先证者的兄弟也是携带者，具有与轻度胶原蛋白VI表型一致的临床特征。在随后的一次怀孕中应要求进行产前诊断时，我们发现胎儿是杂合携带者，这表明它不会受到严重UCMD的影响。COL6A1过早终止突变表现出可变的外显率，因此在遗传咨询时需要谨慎对待。
