Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease most often due to steroid 21-hydroxylase deficiency (21OHD). The incidence of the CYP21A2 gene mutations in 21OHD has been extensively studied in recent years. The p.Q318X mutation presents an ethnic-specific distribution with a higher prevalence (40%) in Tunisia.
Methods: A total of 20 Moroccan patients were studied, using PCR amplification and sequencing, to determine the mutation spectrum and to evaluate whether the incidence of the p.Q318X mutation is similar in Morocco and in Tunisia.
Results: Results revealed that 15 patients were with the salt wasting (SW) form and five with the simple virilizing (SV) form of the disease. All patients were homozygous or compound heterozygous for severe mutations of the CYP21A2 gene. The IVS2-13A/C>G was the most common mutation (47% of chromosomes) and the p.I172N (11%) was associated with the SV form. The p.Q318X was the second most frequent mutation (19.4%) with a regional distribution: the mutation was especially detected (75%) in patients from the midland of Morocco (Fez). We found a novel p.L353R mutation associated with the p.V281L mutation on the same chromosome in one patient at homozygous state.
Conclusions: Genotyping for the four common mutations (IVS2-13A/C>G, p.Q318X, large lesions of the CYP21A2 gene and p.I172N) should allow identifying the diseased alleles and providing genetic counseling in 94% of CAH Moroccan cases. The regional distribution of mutations should help in screening studies.