title: 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.affiliation: Hacettepe University, Department of Pediatric Endocrinology, Ankara, Turkey. Electronic address: nurgun.kandemir@gmail.com.
authors.forename: Nurgun
authors.initials: N
authors.lastname: Kandemir
authors.affiliation: Hacettepe University, Pediatric Metabolism Unit, Institute of Child Health, Ankara, Turkey.
authors.forename: Didem Yucel
authors.initials: DY
authors.lastname: Yilmaz
authors.affiliation: Hacettepe University, Department of Pediatric Endocrinology, Ankara, Turkey.
authors.forename: E Nazli
authors.initials: EN
authors.lastname: Gonc
authors.affiliation: Hacettepe University, Department of Pediatric Endocrinology, Ankara, Turkey.
authors.forename: Alev
authors.initials: A
authors.lastname: Ozon
authors.affiliation: Hacettepe University, Department of Pediatric Endocrinology, Ankara, Turkey.
authors.forename: Ayfer
authors.initials: A
authors.lastname: Alikasifoglu
authors.affiliation: Hacettepe University, Pediatric Metabolism Unit, Institute of Child Health, Ankara, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Dursun
authors.affiliation: Hacettepe University, Pediatric Metabolism Unit, Institute of Child Health, Ankara, Turkey.
authors.forename: R Koksal
authors.initials: RK
authors.lastname: Ozgul
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D005817:Genetic Counseling; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D012189:Retrospective Studies; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*; D014421:Turkey
chemical_list: D013252:Steroid 11-beta-Hydroxylase
keywords: 11beta-hydroxylase deficiency; CYP11B1; CYP11B1 novel mutations; Congenital adrenal hyperplasia