EXCLUSION OF LINKAGE BETWEEN THE COLLAGENASE GENE AND GENERALIZED RECESSIVE DYSTROPHIC EPIDERMOLYSIS-BULLOSA PHENOTYPE

被引:22
作者
HOVNANIAN, A
DUQUESNOY, P
AMSELEM, S
BLANCHETBARDON, C
LATHROP, M
DUBERTRET, L
GOOSSENS, M
机构
[1] CHU HENRI MONDOR,INSERM,U91,F-94010 CRETEIL,FRANCE
[2] HOP ST LOUIS,SERV DERMATOL,F-75010 PARIS,FRANCE
[3] CTR ETUD POLYMORPHISME HUMAIN,F-75475 PARIS 10,FRANCE
关键词
INTRAGENIC POLYMORPHISM; POLYMERASE CHAIN REACTION; DENATURING GRADIENT GEL ELECTROPHORESIS; DIRECT GENOMIC SEQUENCING; LOD SCORE;
D O I
10.1172/JCI115489
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Generalized recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited autosomal disease characterized by dermolytic blister formation. Enhanced collagenase and/or abnormal collagenase have been reported in skin from affected patients, suggesting that collagenase could be responsible for the absence of anchoring fibrils in this disorder. We used a genetic linkage approach to test the hypothesis that this disease is due to a defect in the collagenase gene in nine affected families. Analysis of amplified genomic DNA fragments of the collagenase gene by means of denaturing gradient gel electrophoresis (DGGE) allowed us to detect intragenic polymorphisms, which were subsequently characterized by direct genomic sequencing. Segregation analysis of these polymorphic sites showed exclusion of linkage between the collagenase gene and generalized RDEB phenotype in a family with consanguineous parents and three affected children. However, the possibility of linkage with the collagenase gene in the other eight families tested could not be excluded. The genetic markers described here provide a tool for investigating genetic linkage in other affected families. Overall, our results show that generalized RDEB can be caused by a defect in a gene other than the collagenase gene, and support the hypothesis that the genetic defect lies in abnormal anchoring fibril formation.
引用
收藏
页码:1716 / 1721
页数:6
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