Mucolipidosis in a Chinese family with compound heterozygous mutations at the GNPTAB gene
Mucolipidosis in a Chinese family with compound heterozygous mutations at the GNPTAB gene
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GNPTAB 基因复合杂合突变中国家系粘脂沉积症
DOI：
10.1016/j.cca.2011.04.025
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发表时间：
2011-07-15
影响因子：
5
通讯作者：
Liu, Mugen
中科院分区：
文献类型：
--
作者：
Zhan, Tailan;Cui, Xiukun;Liu, Mugen
背景资料：粘多糖沉积症（MPS）是由一种或多种类型的粘多糖或糖胺聚糖（GAG）的代谢缺陷引起的。粘脂病（ML）是一组遗传性疾病，其中糖胺聚糖（GAGS）和鞘脂在体内积聚。MPS和ML均属于溶酶体贮积病，临床表现相似。这两种类型的疾病的区别并不总是可能使用传统的临床诊断。方法：对临床初步诊断为MPS或ML的先证者，用10个粘多糖沉积症候选基因位点和2个粘脂沉积症候选基因位点的一组微卫星标记进行连锁分析。使用Linkage Package 5.2程序计算两点对数比值（lod）评分。结果：通过连锁分析和突变分析，证实该家系成员存在GNPTAB基因的p.R364X和c.2715 + 1G>A复合杂合突变。结论：本研究证实了ML临床表现中基因型与表型之间的病理关系，提示基于DNA的诊断是一种较好的ML和MPS的诊断方法。(C)2011 Elsevier B.V.保留所有权利。
Background: Mucopolysaccharidoses (MPS) are caused by the deficiency in the metabolism of one or more types of mucopolysaccharides or glycosaminoglycans (GAGs). Mucolipidoses (ML) are a group of genetic disorders in which both glycosaminoglycans (GAGS) and sphingolipids build up in the body. Both of MPS and ML belong to lysosomal storage diseases and show similar clinical manifestations. Distinction of these two types of diseases has not been always possible using conventional clinical diagnoses. Genetic test provides a definitive diagnosis for ML and MPS diseases.Methods: The initial clinical diagnosis had suspected the proband as either MPS or ML To verify the clinical diagnosis, linkage analysis was performed with a panel of microsatellite markers flanking 10 candidate genetic loci for mucopolysaccharidosis and 2 loci for mucolipidosis. Two-point logarithm of odds (lod) scores was calculated using Linkage Package 5.2 program. Direct DNA sequence analyses of GNPTAB in the family members were performed.Results: By using linkage and mutational analyses, we have identified that the family members contain compound heterozygous mutations of p.R364X and c.2715 + 1 G>A in the GNPTAB gene. We determine the family as MLIII based on the DNA-test and clinical diagnoses.Conclusion: Our study confirms the pathological relationship between the patients' genotype and phenotype in the clinical ML manifestation, and suggests that DNA-based diagnosis serves as a better way to define ML and MPS. (C) 2011 Elsevier B.V. All rights reserved.