Genotype-phenotype correlation in hereditary multiple exostoses

被引:139
作者
Francannet, C
Cohen-Tanugi, A
Le Merrer, M
Munnich, A
Bonaventure, J
Legeai-Mallet, L
机构
[1] INSERM, U393, Unite Rech Handicaps Genet & Enfant, F-75743 Paris 15, France
[2] Hop Hotel Dieu, Serv Pediat & Genet B, Clermont Ferrand, France
关键词
hereditary multiple exostoses; EXT1; EXT2; chondrosarcoma;
D O I
10.1136/jmg.38.7.430
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Hereditary multiple exostoses (HME) is a genetically heterogeneous autosomal dominant disorder characterised by the development of bony protuberances mainly located on the long bones. Three HME loci have been mapped to chromosomes 8q24 (EXT1), 11p11-13 (EXT2), and 19p (EXT3). The EXT1 and EXT2 genes encode glycosyltransferases involved in biosynthesis of heparan sulphate proteoglycans. Here we report on a clinical survey and mutation analysis of 42 HME French families and show that EXT1 and EXT2 accounted for more than 90% of HME cases in our series. Among them, 27/42 cases were accounted for by EXT1 (64%, four nonsense, 19 frameshift, three missense, and one splice site mutations) and 9/42 cases were accounted for by EXT2 (21%, four nonsense, two frameshift, two missense, and one splice site mutation). Overall, 31/36 mutations were expected to cause loss of protein function (86%). The most severe forms of the disease and malignant transformation of exostoses to chondrosarcomas were associated with EXT1 mutations. These findings provide the first genotype-phenotype correlation in HME and will, it is hoped, facilitate the clinical management of these patients.
引用
收藏
页码:430 / 434
页数:5
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