Akademik Veri Yönetim Sistemi
54th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE), Barcelona, İspanya, 30 Eylül - 03 Ekim 2015, cilt.84, sa.1, ss.315
Background: Congenital adrenal hyperplasia (CAH) due to
11b-hydroxylase deficiency (11OHD), a rare autosomal recessive
disorder, is the second most common form of CAH, resulting in
glucocorticoid deficiency, hyperandrogenism and hypertension.
Objective and hypotheses: To investigate the specific CAH
mutations in CYP11B1 gene and to examine for genotypephenotype
correlations. Method: 21 patients (nZ9, 46, XX;
nZ12, 46, XY) with the classical 11OHD from 20 unrelated
Turkish families were included in this study. Diagnosis of 11OHD
was based on both clinical and hormonal criteria. Mutation
screening of CYP11B1 gene was performed using direct Sanger
sequencing analysis. Known mutations were confirmed by
database and literature search. Novel mutations were analyzed
by in silico prediction tools (PolyPhen-2, SIFT and Mutation
Taster). Results: The age of diagnosis at onset ranged from 6 days
to 12.5 years. The rate of consanguinity was very high (75%). Four
out of nine 46, XX patients received a late diagnosis (age 2–8.7
years) and were raised as males due to severe masculinization
(Prader genital stages IV and V). Mutation analyses in 20 index
patients revealed 12 different mutations in CYP11B1 gene. These
mutations were homozygous (HM) p.L299P (30%, 6/20), HM
p.R141X (10%, 2/20), HM c.954GOA (silence, cryptic splicing;
10%, 2/20), HM IVS8C2TOC (novel splice-donor mutation, 5%,
1/20), compound heterozygous (CHT)((p.L299P)C(IVS8C2TO
C); 5%, 1/20), HM p.W116C (5%, 1/20), HM p.R384Q (5%, 1/20),
HM p.R448C (5%, 1/20), HM c.1449_1451delGGT (5%, 1/20),
CHT ((G393CAG)C(p.L299P)); 5%, 1/20), HM
c.1179_1180dupGA (novel; 5%, 1/20) and HM p.R143P (novel
missense; 5%, 1/20). One patient had mutation in only one allele
(p.T318M). There was no definitive correlation between genotype
and phenotype. Conclusion: In this study, three different novel
mutations were detected and the p.L299P was found to be the most
common mutation. The results of the study might contribute to
the establishment of molecular screening strategies. Identification
of the disease causing mutations provides reliable information for
genetic counseling for the families.