Mucolipidosis type IV:: Novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population
Mucolipidosis type IV:: Novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population
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DOI：
10.1002/humu.1115
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发表时间：
2001-01-01
期刊：
影响因子：
3.9
通讯作者：
Bach, G
中科院分区：
文献类型：
--
作者：
Bargal, R;Avidan, N;Bach, G
MCOLN1基因在黏液脂质病IV型（MLIV）中发生突变，这是一种神经退行性、隐性、溶酶体储存疾病。这种疾病在德系犹太人中发病率相对较高，这是由于两种创始突变构成了该人群中95%的MLIV等位基因[Bargal等，2000]。在本报告中，我们完成了对犹太和非犹太MLIV患者的突变分析，这些患者的DNA是我们可以获得的。在严重感染患者的A MCOLN1中发现了4个新的突变：2个错义，T232P和F465L；废话，R322X；在第12外显子有11马力的插入。无义突变（R322X）在MCOLN1染色体区域两名不同单倍型的无亲缘关系患者中被发现，表明该CpG位点存在突变热点。一个框架内缺失（F308del）在一个不寻常的轻度精神运动迟缓患者中被发现。MLIV在普通犹太德系犹太人群体中的频率是通过对2000名匿名的、不相关的个体进行两种创始突变分析来估计的。分析表明杂合子频率约为1/100。提出了MCOLN1突变的首选核苷酸编号系统，并讨论了在犹太德系犹太人中检测高风险家庭的筛选程序问题。[j] .生物工程学报，2001。(C) 2001 Wiley-Liss, Inc。
The gene MCOLN1 is mutated in Mucolipidosis type IV (MLIV), a neurodegenerative, recessive, lysosomal storage disorder. The disease is found in relatively high frequency among Ashkenazi Jews due to two founder mutations that comprise 95% of the MLIV alleles in this population [Bargal et al., 2000]. In this report we complete the mutation analysis of Jewish and non-Jewish MLIV patients whose DNA were a available to us. Four novel mutations were identified in the A MCOLN1 gone of severely affected patients: two missense, T232P and F465L; a nonsense, R322X; and an 11-hp insertion in exon 12. The nonsense mutation (R322X) was identified in two unrelated patients with different haplotypes in the MCOLN1 chromosomal region, indicating a mutation hotspot in this CpG site. An in frame deletion (F308del) was identified in a patient with unusual mild psychomotor retardation. The frequency of MLIV in the general Jewish Ashkenazi population was estimated in a sample of 2,000 anonymous, unrelated individuals assayed for the two founder mutations. This analysis indicated a heterozygotes frequency of about 1/100. A preferred nucleotide numbering system for MCOLN1 mutations is presented and the issue of a screening program for the detection of high risk families in the Jewish Ashkenazi population is discussed. Hum Mutat 17:397-402, 2001. (C) 2001 Wiley-Liss, Inc.