Mutation Analysis of Type II Gaucher Disease in Five Taiwanese Children: Identification of Two Novel Mutations

第二型高雪氏症的突變分析

蔡輔仁(Fuu-Jun Tsai) ； 李正淳(Cheng-Chun Lee) ； 吳玫珍(Mei-Chen Wu) ； 林炫沛(Shuan-Pei Lin) ； 林清淵(Ching-Yuang Lin) ； 蔡長海(Chang-Hai Tsai) ； 児玉浩子(Hiroko Kodama) ； 鄔哲源(Jer-Yuarn Wu)

《Acta Paediatrica Taiwanica》 42卷4期 (2001/08) Pp. 231-235

https://doi.org/10.7097/APT.200108.0231

摘要

高雪氏症是常見的脂質貯稱症，起因於溶小體中的acid β-glucosidase(GBA)缺乏，臨床上依神經症狀的有無分爲三型，其中以第二型最爲罕見，但症狀卻最嚴重，通常病童會在兩歲前死亡。利用聚合酶鏈反應及直接定序分析了5名第二型高雪氏症病人的GBA基因突變。結果顯示有90％的突變點可被確認，其中G355D及M241-242ins是新的突變點，所有的病人都攜帶一個L444P突變，而RecNci I突變則佔了20％。利用酵素內切法來分析突變點可能會無法完全掌握高雪氏症病人真正基因型，因此全基因定序是目前分析高雪氏症基因突變的最好方法。

關鍵字

第二型高雪氏症 ； acid β-glucosidase(GBA) ； 突變

並列摘要

Gaucher disease (GD), one of the most prevalent lysosomal storage diseases, is caused by deficiency of lysosomal acid beta-glucosidase (GBA). It is divided into three types according to the presence and progression of neurologic symptoms. Of those, type II is relatively rare and most severe; patients usually die before the age of two years. Using polymerase chain reaction (PCR) and direct sequencing of GBA gene in five Taiwanese type II GD patients, we identified two novel mutations: G355D and threenucleotjde insertion in exon 7 of GBA. The latter resulted in an in-frame insertion of a methionine residue between Leu241 and Ser242. L444P, the second most common GD allele among non-Jewish Caucasian population, was found in all five type II GD patients (50%). Overall, 9 out of 10 GD alleles were identified in this study. Direct sequencing of all PCR products led to high detection rate of GD alleles and identification of the RecNci I alleles. In the future, high throughput sequencing will make it possible identifying more rare mutations in type II GD patients.

並列關鍵字

type II Gaucher disease ； acid beta-glucosidase (GBA) ； mutation