Xiang F, Almqvist E W, Huq M, Lundin A, Hayden M R, Edström L, Anvret M, Zhang Z
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Am J Hum Genet. 1998 Nov;63(5):1431-8. doi: 10.1086/302093.
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations. The disease is associated with a CAG trinucleotide-repeat expansion in the Huntington gene (IT15) on chromosome 4p16.3. One family with a history of HD was referred to us initially for predictive testing using linkage analysis. However, the chromosome 4p region was completely excluded by polymorphic markers, and later no CAG-repeat expansion in the HD gene was detected. To map the disease trait segregating in this family, whole-genome screening with highly polymorphic dinucleotide-, trinucleotide-, and tetranucleotide-repeat DNA markers was performed. A positive LOD score of 3.01 was obtained for the marker D20S482 on chromosome 20p, by two-point LOD-score analysis with the MLINK program. Haplotype analysis indicated that the gene responsible for the disease is likely located in a 2.7-cM region between the markers D20S193 and D20S895. Candidate genes from the mapping region were screened for mutations.
亨廷顿舞蹈病（HD）是一种常染色体显性神经退行性疾病，其特征为运动障碍、认知丧失和精神症状。该疾病与位于4号染色体p16.3区域的亨廷顿基因（IT15）中的CAG三核苷酸重复序列扩增有关。最初，一个有HD病史的家庭被转介给我们，以通过连锁分析进行预测性检测。然而，4号染色体p区域被多态性标记完全排除，后来在HD基因中未检测到CAG重复序列扩增。为了定位该家族中分离的疾病性状，我们使用高度多态性的二核苷酸、三核苷酸和四核苷酸重复DNA标记进行了全基因组筛查。通过使用MLINK程序进行两点LOD评分分析，在20号染色体p上的标记D20S482处获得了3.01的阳性LOD评分。单倍型分析表明，导致该疾病的基因可能位于标记D20S193和D20S895之间的2.7厘摩区域内。我们对来自定位区域的候选基因进行了突变筛查。
