Clinical and genetic characterization of Chanarin-Dorfman syndrome patients: first report of large deletions in the ABHD5 gene.
Clinical and genetic characterization of Chanarin-Dorfman syndrome patients: first report of large deletions in the ABHD5 gene.
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DOI：
10.1186/1750-1172-5-33
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发表时间：
2010-12-01
影响因子：
3.7
通讯作者：
Tavian D
中科院分区：
文献类型：
--
作者：
Redaelli C;Coleman RA;Moro L;Dacou-Voutetakis C;Elsayed SM;Prati D;Colli A;Mela D;Colombo R;Tavian D
Chanarin-Dorfman综合征（CDS）是一种罕见的常染色体隐性遗传疾病，其特征是非大疱性先天性鱼鳞病样红皮病（NCIE）和大多数组织中三酰甘油（TG）液滴的细胞内积聚。临床表型涉及多个器官和系统，包括肝脏、眼、耳、骨骼肌和中枢神经系统（CNS）。ABHD 5/CGI 58基因突变与CDS相关。来自地中海国家的六个不同家族的八名CDS患者被招募进行遗传研究。ABHD 5基因的分子分析包括7个编码外显子和推定的5'调控区的测序，以及正常和异常ABHD 5 cDNA的逆转录-聚合酶链反应分析和测序。共鉴定出5个不同的突变，其中4个是新的，包括两个剪接位点突变（c.47+1G>A和c.960+5G>A）和两个大缺失（c.898_* 320 del和c.662-1330_773+ 46 del）。所有报道的突变都被预测为致病性的，因为它们导致早期终止密码子或移码产生翻译的提前终止。虽然在CDS患者中已经鉴定出无义、错义、移码和剪接位点突变，但以前没有描述过大的基因组缺失。这些结果强调需要一种有效的方法进行基因组缺失筛选，以确保准确的分子诊断CDS。此外，尽管进行了密集的分子筛选，但在一名确诊为CDS的临床诊断患者中未发现突变，这与该综合征的遗传异质性有关。
Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disorder characterized by nonbullous congenital ichthyosiform erythroderma (NCIE) and an intracellular accumulation of triacylglycerol (TG) droplets in most tissues. The clinical phenotype involves multiple organs and systems, including liver, eyes, ears, skeletal muscle and central nervous system (CNS). Mutations in ABHD5/CGI58 gene are associated with CDS. Eight CDS patients belonging to six different families from Mediterranean countries were enrolled for genetic study. Molecular analysis of the ABHD5 gene included the sequencing of the 7 coding exons and of the putative 5' regulatory regions, as well as reverse transcript-polymerase chain reaction analysis and sequencing of normal and aberrant ABHD5 cDNAs. Five different mutations were identified, four of which were novel, including two splice-site mutations (c.47+1G>A and c.960+5G>A) and two large deletions (c.898_*320del and c.662-1330_773+46del). All the reported mutations are predicted to be pathogenic because they lead to an early stop codon or a frameshift producing a premature termination of translation. While nonsense, missense, frameshift and splice-site mutations have been identified in CDS patients, large genomic deletions have not previously been described. These results emphasize the need for an efficient approach for genomic deletion screening to ensure an accurate molecular diagnosis of CDS. Moreover, in spite of intensive molecular screening, no mutations were identified in one patient with a confirmed clinical diagnosis of CDS, appointing to genetic heterogeneity of the syndrome.
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影响因子：
9.8
作者：
Lefevre, C;Jobard, F;Fischer, J
通讯作者：
Fischer, J
影响因子：
--
作者：
Wollenberg, A;Schaller, M;Wolff, H
通讯作者：
Wolff, H
DOI：
10.1097/00005176-199711000-00011
发表时间：
1997-11-01
影响因子：
2.9
作者：
Igal, RA;Rhoads, JM;Coleman, RA
通讯作者：
Coleman, RA
影响因子：
30.8
作者：
Fischer, Judith;Lefevre, Caroline;Salvayre, Robert
通讯作者：
Salvayre, Robert
影响因子：
29
作者：
Lass, Achim;Zimmermann, Robert;Zechner, Rudolf
通讯作者：
Zechner, Rudolf