Novel and prevalent CYP11B1 gene mutations in Turkish patients with 11-β hydroxylase deficiency.

Abstract

11β-Hydroxylase deficiency is the second most frequent type of congenital adrenal hyperplasia and is more common in those of Turkish descent than in other populations. The purpose of this study is to examine the spectrum of CYP11B1 gene mutations in Turkish patients with 11β-hydroxylase deficiency. Twenty-eight patients from 24 families, ages ranging from 0.1 to 7 years, were included in the study. Clinical diagnosis was based on virilization and high levels of 11-deoxycortisol. Twenty-six cases exhibited the classical and 2 cases the non-classical form. Mutation screening of 9 CYP11B1 exons was performed by direct DNA sequence analysis, specifically amplifying CYP11B1 gene fragments while avoiding simultaneous amplification of homologous CYP11B2 gene sequences. Seventeen different mutations were detected, 6 of which are novel (p.Gln189Hisfs*70, p.Glu198Gly, p.Thr318Lys, p.Gly446Ser, IVS8+5G>C and exon 3-5 del). All of the identified mutations resulted in the classical form with severe virilization, except for the p.Gly446Ser mutation, which caused a late-onset type of 11β-hydroxylase deficiency. The c.954G>A;p.Thr318Thr mutation was the most common in our cohort, with an allele frequency of 14.6%.Of the CYP11B1 gene mutations detected, 75% were found in exons 3, 5 and 7 and the half of the mutations were nonsense, splice site, deletion or insertion mutations, causing severe virilization in female patients. The findings are important for genetic counseling and the prenatal diagnosis of Turkish patients with 11β-hydroxylase deficiency.

• Authors: Nurgun Kandemir, Didem Yucel Yilmaz, E Nazli Gonc, Alev Ozon, Ayfer Alikasifoglu, Ali Dursun, R Koksal Ozgul
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 165 Issue Pt A Pg. 57-63 (01 2017) ISSN: 1879-1220 [Electronic] England
• PMID: 26956189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Steroid 11-beta-Hydroxylase

Topics

• Adrenal Hyperplasia, Congenital (genetics)
• Binding Sites
• Child
• Child, Preschool
• Exons
• Female
• Genetic Counseling
• Genotype
• Humans
• Infant
• Infant, Newborn
• Male
• Mutation
• Phenotype
• Prevalence
• Retrospective Studies
• Steroid 11-beta-Hydroxylase (genetics)
• Turkey