CYP11B1 gene mutations in patients congenital adrenal hyperplasia in Turkey

Baş F. , Ergun-Longmire B., Saka N., Toksoy G. , Uyguner Z. O. , Poyrazoğlu Ş. , ...More

54th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE), Barcelona, Spain, 30 September - 03 October 2015, vol.84, no.1, pp.315

  • Publication Type: Conference Paper / Summary Text
  • Volume: 84
  • City: Barcelona
  • Country: Spain
  • Page Numbers: pp.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.