Levodopa-responsive dystonia -: GTP cyclohydrolase I or parkin mutations?
Levodopa-responsive dystonia -: GTP cyclohydrolase I or parkin mutations?
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DOI：
10.1093/brain/123.6.1112
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发表时间：
2000-06-01
期刊：
影响因子：
14.5
通讯作者：
Brice, A
中科院分区：
文献类型：
--
作者：
Tassin, J;Dürr, A;Brice, A
常染色体显性多巴反应性肌张力障碍（DRD）通常由编码鸟苷三磷酸环水解酶I （GTPCH I）的基因突变引起。通过对GTPCH I基因6个编码外显子、5′-未翻译区和外显子-内含子边界的测序，研究了22个左旋多巴反应性肌张力障碍表型的家族，在12个家族中发现了11个杂合突变，包括5个错义突变、1个剪接位点突变、2个小缺失和2个无义突变，其中27例患者和13例无症状携带者，6个突变为新突变，5个突变已被报道。其中四个突变导致GTPCH I蛋白的截断，一个家族在5'-非翻译区携带碱基对变化，在对照组中未检测到，这可能是导致表型的原因，其余10个家族中有3个在6号染色体上的parkin基因缺失，这表明在某些情况下区分DRD和parkin突变是非常困难的。临床谱系从经典的DRD表型扩展到帕金森病伴左旋多巴诱导的运动障碍，包括痉挛性截瘫和无肌张力障碍。
Autosomal dominant DOPA-responsive dystonia (DRD) is usually caused by mutation in the gene encoding guanosine triphosphate-cyclohydrolase I (GTPCH I). We studied 22 families with a phenotype of levodopa-responsive dystonia by sequencing the six coding exons, the 5'-untranslated region and the exon-intron boundaries of the GTPCH I gene, Eleven heterozygous mutations were identified, including five missense mutations, one splice site mutation, two small deletions and two nonsense mutations, in 12 families that included 27 patients and 13 asymptomatic carriers, Six mutations were new and five had already been reported, Four of the mutations caused truncation of the GTPCH I protein, One family carried a base-pair change in the 5'-untranslated region, not detected in controls, that could be responsible for the phenotype, Three of the remaining 10 families had deletions in the parkin gene on chromosome 6, underlining how difficult it is to distinguish, in some cases, between DRD and parkin mutations, No mutations were identified in seven families, The clinical spectrum extended from the classical DRD phenotype to parkinsonism with levodopa-induced dyskinesias, and included spastic paraplegia as well as the absence of dystonia.