Chamberlain S, Shaw J, Rowland A, Wallis J, South S, Nakamura Y, von Gabain A, Farrall M, Williamson R
Department of Biochemistry and Molecular Genetics, Saint Mary's Hospital Medical School, University of London.
Nature. 1988 Jul 21;334(6179):248-50. doi: 10.1038/334248a0.
Friedreich's ataxia is an autosomal recessive disease with progressive degeneration of the central and peripheral nervous system. The biochemical abnormality underlying the disorder has not been identified. Prompted by the success in localizing the mutations causing Duchenne muscular dystrophy, Huntington's disease and cystic fibrosis, we have undertaken molecular genetic linkage studies to determine the chromosomal site of the Friedreich's ataxia mutation as an initial step towards the isolation and characterization of the defective gene. We report the assignment of the gene mutation for this disorder to chromosome 9p22-CEN by genetic linkage to an anonymous DNA marker MCT112 and the interferon-beta gene probe. In contrast to the clinical variation seen for the disorder, no evidence of genetic heterogeneity is observed.
弗里德赖希共济失调是一种常染色体隐性疾病,会导致中枢和周围神经系统进行性退化。该疾病潜在的生化异常尚未明确。鉴于在确定导致杜氏肌营养不良症、亨廷顿舞蹈症和囊性纤维化的突变位置方面取得的成功,我们开展了分子遗传连锁研究,以确定弗里德赖希共济失调突变的染色体位置,作为分离和鉴定缺陷基因的第一步。我们报告,通过与一个匿名DNA标记MCT112和干扰素-β基因探针进行遗传连锁,该疾病的基因突变被定位于9号染色体p22 - 着丝粒区域。与该疾病所呈现的临床变异不同,未观察到遗传异质性的证据。