Abstract:
: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.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Francannet C,Cohen-Tanugi A,Le Merrer M,Munnich A,Bonaventure J,Legeai-Mallet Ldoi
10.1136/jmg.38.7.430keywords:
subject
Has Abstractpub_date
2001-07-01 00:00:00pages
430-4issue
7eissn
0022-2593issn
1468-6244journal_volume
38pub_type
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更新日期:1994-01-01 00:00:00
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更新日期:1992-02-01 00:00:00
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journal_title:Journal of medical genetics
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pub_type: 杂志文章,评审
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更新日期:1990-02-01 00:00:00
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pub_type: 杂志文章,实务指引
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