X-linked recessive chondrodysplasia punctata: Spectrum of arylsulfatase E gene mutations and expanded clinical variability
X-linked recessive chondrodysplasia punctata: Spectrum of arylsulfatase E gene mutations and expanded clinical variability
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DOI：
10.1002/ajmg.a.10950
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发表时间：
2003-03-01
影响因子：
2
通讯作者：
Parenti, G
中科院分区：
文献类型：
--
作者：
Brunetti-Pierri, N;Andreucci, MV;Parenti, G
X连锁点状软骨发育不良（CDPX 1），由于芳基硫酸酯酶E（ARSE）基因突变，是一种先天性疾病，其特征是软骨和骨发育异常。我们对16名男性患者的ARSE基因进行了突变分析，在12名受试者中发现了突变。在患者中观察到临床变异性，包括其中一名患者的严重表现和早期致死性，以及白内障和呼吸窘迫等症状。这表明CDPX 1的临床谱，通常被认为是一种相对温和的点状软骨发育不良，比以前报道的更广泛。在检查的患者中发现了不同类型的突变。在Cos 7细胞中表达三个错义突变（I80 N、T481 M、P578 S）以研究对芳基硫酸酯酶E催化活性的影响。这些突变导致酶活性受损，表明它们是导致疾病的原因。发现两个无义突变，4例为W581 X，1例为R540 X，1例为插入（T616 ins）。在3例患者中，我们发现了ARSE基因的缺失：在1例患者中，缺失仅涉及基因的3'端，而在2例患者中，ARSE基因完全缺失。(C)2003 Wiley-Liss，Inc.
X-linked chondrodysplasia punctata (CDPX1), due to mutations of the arylsulfatase E (ARSE) gene, is a congenital disorder characterized by abnormalities in cartilage and bone development. We performed mutational analysis of the ARSE gene in a series of 16 male patients, and we found mutations in 12 subjects. Clinical variability was observed among the patients, including severe presentations with early lethality in one of them, and symptoms such as cataract and respiratory distress. This indicates that the clinical spectrum of CDPX1, commonly considered a relatively mild form of chondrodysplasia punctata, is wider than previously reported. Different types of mutations were found among the patients examined. Three missense mutations (I80N, T481M, P578S) were expressed in Cos7 cells to study the effects on arylsulfatase E catalytic activity. These mutations caused impaired enzymatic activity suggesting that they are responsible for the disease. Two nonsense mutations, W581X in four patients and R540X in one, were found. One patient showed an insertion (T616ins). In three patients we found deletions of the ARSE gene: in one the deletion involved only the 3' end of the gene, while in two the ARSE gene was completely deleted. (C) 2003 Wiley-Liss, Inc.