Mavridou I, Cozar M, Douzgou S, Xaidara A, Lianou D, Vanier M T, Dimitriou E, Grinberg D, Vilageliu L, Michelakakis H
Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
Clin Genet. 2014 Jun;85(6):543-7. doi: 10.1111/cge.12200. Epub 2013 Jun 12.
Niemann-Pick type C (NPC) disease is a rare autosomal recessive lysosomal storage disease, exhibiting an extremely heterogeneous clinical phenotype. It is a cellular lipid trafficking disorder characterized by the accumulation in the lysosomal/late endosomal system of a variety of lipids, especially unesterified cholesterol. So far two genes, NPC1 or NPC2, have been linked to the disorder. It is a panethnic disease for which two isolates have been described. We present a novel NPC1 mutation (p.A1132P; c.3394G>C) identified in homozygosity in two patients originating from the same small town of an Aegean Sea island and the results of the broad screening of their extended families. Overall 153 individuals have so far been investigated and a total of 64 carriers were identified. Moreover a common descent of the individuals tested was revealed and all carriers could be traced back to a common surname, apparently originating from a common ancestor couple six generations back. The mutation was found associated with an uncommon haplotype in the island that is also present in other populations.
尼曼-匹克C型（NPC）病是一种罕见的常染色体隐性溶酶体贮积病，临床表现极为异质性。它是一种细胞脂质转运障碍疾病，其特征是多种脂质在溶酶体/晚期内体系统中蓄积，尤其是未酯化胆固醇。迄今为止，已发现两个基因NPC1或NPC2与该病相关。这是一种泛种族疾病，已描述了两个隔离群。我们报告了在来自爱琴海岛同一小镇的两名患者中纯合鉴定出的一种新型NPC1突变（p.A1132P；c.3394G>C）及其大家庭的广泛筛查结果。到目前为止，共调查了153人，共鉴定出64名携带者。此外，还揭示了受测个体的共同血统，所有携带者都可追溯到一个共同姓氏，显然起源于六代以前的一对共同祖先。该突变与该岛一种罕见的单倍型相关，这种单倍型在其他人群中也存在。
