Ouahchi K, Arita M, Kayden H, Hentati F, Ben Hamida M, Sokol R, Arai H, Inoue K, Mandel J L, Koenig M
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS, INSERM, ULP), Illkirch, Strasbourg, France.
Nat Genet. 1995 Feb;9(2):141-5. doi: 10.1038/ng0295-141.
Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive neurodegenerative disease which maps to chromosome 8q13. AVED patients have an impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the alpha-tocopherol transfer protein (alpha-TTP). Here we report the identification of three frame-shift mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mutation correlates with a severe phenotype but alters only the C-terminal tenth of the protein. Two other mutations were found in single families. The finding of alpha TTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.
单纯维生素E缺乏性共济失调（AVED）是一种常染色体隐性神经退行性疾病，定位于8号染色体q13区域。AVED患者将α-生育酚整合到肝脏分泌的脂蛋白中的能力受损，该功能被认为归因于α-生育酚转运蛋白（α-TTP）。在此，我们报告在α-TTP基因中鉴定出三个移码突变。在分析的17个家族中，744delA突变占突变等位基因的68%，且似乎已在北非和意大利传播。该突变与严重表型相关，但仅改变蛋白质的C末端十分之一。在单个家族中发现了另外两个突变。在AVED患者中发现α-TTP基因突变证实了维生素E作为该疾病神经损伤保护剂的治疗作用。
