ESPE Abstracts

Background: Deficiency of 11β-hydroxylase is the second most frequent type of congenital adrenal hyperplasia and more common in Turkey than other populations.

Objective and hypotheses: The purpose of this study is to examine the spectrum of CYP11B1 gene mutations in Turkish population.

Method: 17 patients from 13 families are included in this study. Diagnosis was based on virilisation and high levels of 11-deoxycortisol. 15 cases had classical and two cases had non-classical form. Mutation screening of nine exons in CYP11B1 gene was performed using direct sequence analysis. The CYP11B1 gene was specifically amplified avoiding simultaneous amplification of homologous CYP11B2 gene sequences.

Results: The karyotype of nine cases out of 15 was 46,XX and the remaining was 46,XY. The age at diagnosis ranged 0.1-4.2 years. 46,XX cases presented with severe virilisation (Prader genital stages IV and V). Four of 46,XX patients were reared as male at presentation and three of them remained male due to establishment of male gender identity. Two siblings with late onset form were diagnosed at 4, 9, and 7 years. Overall mutation analyses revealed eight homozygous pathogenic mutations of four different types (two splicing, two duplication, two nonsense, and two missense). The detected nucleotide changes in patients resulted in five novel (c.1336G>A;p.G446S, c.563_566dupTCCA, c.1200+1G>A, c.1398+5G>C, c.1178-1179dupAG) and three previously reported mutations (p.A141X, p.L299P, and p.A384Q) in the CYP11B1 gene. Mutation prediction software tools PolyPhen-2andSIFT, both indicate that the novel mutations detected in this study are likely to be pathogenic.

Conclusion: All detected mutations were scattered throughout the gene. The most common mutation in this group of Turkish patients was A141X with the allele frequency of 25%. All new and known mutations in the classical form led to severe virilisation. The missense novel mutation c.1336GA;p.GLY446Ser caused late onset form of the disease.