RENAL-ARTERY FIBROMUSCULAR DYSPLASIA - FAMILIAL CASES AND GENETIC APPROACH

The aim of this study was to conduct a formal pedigree analysis of the involvement of the elastin gene in families. From 140 subjects with r enal FMD documented on angiography, family cases with documented renal artery fibromuscular dysplasia (FMD) and to test pedigrees were const ructed and familial cases defined by angiographic evidence of FMD in a t least one sibling. Familial screening was made either by echodoppler for asymptomatic subjects or by digital intravenous angiography for h ypertensive subjects. Linkage analysis at the elastin gene locus was p erformed in these families with two polymorphic markers : one dialleli c RFLP located in exon 16 and one multiallelic CA repeat located in in tron 17 of the elastin gene. Fourteen pedigrees (10 %) were obtained i ncluding nine sibling pairs, four trios and one vertical transmission from a father to his daughter. Most affected subjects were females (84 %) but familial cases were more frequently bilateral than sporadic ca ses (80 % vs 49 %, p = 0.07). Pedigrees analysis was compatible with a n autosomal dominant mode of inheritance and suggested in these famili es an age and sex-dependent incomplete penetrance model. Linkage analy sis resulted in a maximum two-point lod score of 0.06 at theta = 0.20 using the dinucleotide CA repeat. Analysis of the diallelic marker rev ealed similar frequencies in affected and non affected subjects, This study highlights the role of genetics factors in approximately 10 % of FMD cases. The elastin gene does not seem to be involved in the patho genesis of FMD.