CHARACTERIZATION OF STEROID 21-HYDROXYLASE GENE-MUTATIONS IN A OLIGOSYMPTOMATIC FORM OF CONGENITAL ADRENAL-HYPERPLASIA - FAMILY STUDY

BACKGROUND: 21-hydroxilase deficiency accounts for over 90% of all cas es of congenital adrenal hyperplasia (CAH). There is a non-negligible incidence of both severe and nonclassical forms of this genetic disord er. Enzyme deficiency is due to mutations in the gene encoding adrenal 21-hydroxylase (named CYP 21B) and is inherited in an autosomical rec esive way. Complete or partial impairment of enzyme activity has been correlated with the different clinical forms of the disease. PATIENTS AND METHODS: In the present paper CYP 218 gene analysis results obtain ed in a family with two kindred affected by a nonclassical form of the disease are shown. Clinical assessment of these two kindred showed a very mild form of the disease, whereas biochemical results suggested a late-onset partial 21-hydroxylase deficiency. Genotyping for deletion s and 10 point mutations in the CYP 218 gene was performed by Southern blot analysis and polymerase chain reaction (PCR) allele-specific oli gonucleotide (ASO) hybridation technique. RESULTS: Molecular genetic a nalysis performed in the two affected patients and two further relativ es allowed us to detect the presence of different mutations in the two alleles of the CYP 218 gene. One of these mutations was severe (655G) and came from maternal line, whereas the other was mild (Val281Leu) a nd originated in paternal line. CONCLUSION: Molecular genetic analysis allows the possibility of finding severe (and non-expected) mutations in patients with clinically mild and late-onset forms of the 21-hydro xylase deficiency.