Furukawa Y, Guttman M, Sparagana S P, Trugman J M, Hyland K, Wyatt P, Lang A E, Rouleau G A, Shimadzu M, Kish S J
Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada.
Ann Neurol. 2000 Apr;47(4):517-20.
Although it is assumed that most patients with autosomal dominant dopa-responsive dystonia (DRD) have a GTP cyclohydrolase I dysfunction, conventional genomic DNA sequencing of the gene (GCH1) coding for this enzyme fails to reveal any mutations in about 40% of DRD patients, which makes molecular genetic diagnosis difficult. We found a large heterozygous GCH1 deletion, which cannot be detected by the usual genomic DNA sequence analysis, in a three-generation DRD family and conclude that a large genomic deletion in GCH1 may account for some "mutation-negative" patients with dominantly inherited DRD.
尽管假定大多数常染色体显性遗传性多巴反应性肌张力障碍（DRD）患者存在GTP环化水解酶I功能障碍，但编码该酶的基因（GCH1）的常规基因组DNA测序在约40%的DRD患者中未发现任何突变，这使得分子遗传学诊断变得困难。我们在一个三代DRD家族中发现了一个大的杂合性GCH1缺失，这是常规基因组DNA序列分析无法检测到的，我们得出结论，GCH1中的大基因组缺失可能是一些“无突变”的显性遗传性DRD患者的病因。
