Mutational analysis in Lebanese patients with congenital adrenal hyperplasia due to a deficit in 21-hydroxylase

Molecular defects in the gene encoding steroid 21-hydroxylase (CYP21) resul t in impairment of adrenal steroid synthesis in patients affected with auto somal-recessive congenital adrenal hyperplasias (CAH). In this study, we re port on the molecular screening of six point mutations, large deletions, ge ne conversion events and duplications in 25 unrelated Lebanese families aff ected by CAH due to steroid 21-hydroxylase. The methods used (PCR-digestion and southern blot) allowed the detection of 96% of the disease chromosomes . In classical forms, the most frequent mutation was the splice site mutati on in intron 2 accounting for 39% of the disease alleles. Gene conversion e vents accounted for 14% of the alleles, but no large deletions were found. In nonclassical forms, the V281L mutation in exon 7 represent 86% of the te sted alleles. Genotype-phenotype correlations were as expected: Delta 8nt, Q318X and gene conversion correspond to SW forms, whereas the intron 2 spli ce site mutation may give either SW or SV forms; the V281L mutation was res ponsible for nonclassical forms. The spectrum of mutations underlines the g enetic diversity of the Lebanese population. No correlation could be drawn out between mutations and some specific religious communities, except for t he Delta 8nt mutation, which is present only in the Christian Maronite grou p. Molecular study of the CYP21 gene mig ht constitute a good support for c linicians, especially in consanguineous families, for whom we could provide genetic counselling. Copyright (C) 2000 S. Karger AG, Basel.