Search

Background: Given the rarity of 11β-hydroxylase deficiency (11βOHD), there is a paucity of the data about the differences in clinical and biochemical characteristics of classic (C-11βOHD) and non-classic 11βOHD (NC-11βOHD).Objective: To characterize a multicenter pediatric cohort with 11βOHD. Method: The clinical and biochemical characteristics were retrieved. CYP11B1 gene sequencing was performed. Seventeen plasma steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. Results: 102 patients (C-11βOHD; n=92, NC-11βOHD; n=10) from 76 families (46,XX; n=53) had biallelic CYP11B1 mutations (novel 9 out of 30). Five 46,XX patients (10%) were raised as males. Nineteen patients (19%) had initially been misdiagnosed with 21-hydroxylase deficiency. Female final height was 152 cm (-1.85SDS) and male 160.4 cm (-2.56SDS). None of the NC-11βOHD girls had ambiguous genitalia (C-11βOHD 100%) and none of the NC-11βOHD patients were hypertensive (C-11βOHD 50%). Compared to NC-11βOHD, C-11βOHD patients were diagnosed earlier (1.33 vs. 6.9 years, p 2.2

Mutations in Connexin 26 (Cx26) play an important role in autosomal non-syndromic hereditary hearing toss. In this study, our objective was to find out the significance of Cx26 mutations in Turkish families who had hereditary deafness. Fourteen families who had at least two prelingually deaf children per family were included in the study. One affected child from each of the 14 families was selected for single-stranded conformational polymorphism SSCP analysis. Three PCR reactions were used for each subject to amplify the entire Cx26 coding region with overlap. PCR products were sequenced on an Applied Biosystems (ABI) model 3700 automated sequencer. Six of the 14 representative family members (42.9%) demonstrated shifts on SSCP and were subsequently sequenced for Exons 1 and 2 of GJB2 and were tested for the 432 kb upstream deletion. No mutations were found in Exon I and no 432 kb deletions were noted. Three different GJB2 mutations were found in Exon 2 of the probands, which were 35delG, 299-300delAT, and 487G>A (M163V). GJB2 mutations were detected in 21.4% of the families. Two patients were homozygous for 35delG and 299-300delAT mutations, and were given a diagnosis of DFNB1 deafness (14.3%). two different polymorphisms, 457G>A (V1531) and 380G>AG (R127H) were also found. In conclusion, although GJB2 mutations were detected in 21.4% of the families tested, only 14.3% of subject representatives were homozygous and therefore deafness caused by Cx26 mutation segregated with DFNB1. Thus, contribution of GJB2 mutations appears less significant in familial deafness. This necessitates further assessment for the other known gene regions as well as a search for new genetic factors in familial type of genetic deafness. (C) 2003 Elsevier Ireland Ltd. All rights reserved.