ESPE Abstracts

Background: Mutations in CYP21A2 are the most common cause of congenital adrenal hyperplasia (CAH). Even though disease linked mutations are rarely classified as founder, in this study, we describe a novel founder mutation, c.2T>C (p.M1?), inactivating the translation initiation codon.

Objective and Hypotheses: We aimed to investigate genotype–phenotype correlation and population based origin of this novel mutation in CAH patients with 21-hydroxylase deficiency.

Method: Mutation analyses of CYP21A2 were performed by long PCR–RFLP and Southern blot for detecting large rearrangements. In addition, DNA sequencing was done for detection of point mutations in all patients who live in the northern coastal region of the Black Sea in Turkey.

Results: We describe a novel founder mutation, c.2T>C (p.M1?), inactivating the translation initiation codon. This founder mutation was found as homozygous in ten patients who belong to seven families. All families were from the same small town of whom six of them had consanguinity. Among ten patients, nine of the patients had severe salt-wasting form of CAH and one had simple-virilising form.

Conclusion: Most of our patients have had severe salt-wasting form of disease, which was thought to be consistent with the severe nature of this novel mutation. Though one of the patients who also was homozygous for this mutation, had simple-virilising form of the disease. The genotype–phenotype discordance of this patient requires further explanation.