Familial pericentric inversion chromosome 3 and R448C mutation of CYP11B1 gene in Turkish kindred with 11β-hydroxylase deficiency

11β-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia (CAH). This isoenzyme is coded by two highly homologous genes of cytochrome P450: CYP11B1 and CYP11B2 which were mapped to the chromosomal band 8q24. The aim of this study was to perform a series of molecular and cytogenetic analyses in two families with 11 β-hydroxylase deficiency of the Turkish kindred. Mutational analysis was carried out by directly sequencing the PCR products of CYP11B1 gene. We performed fluorescence in situ hybridisation (FISH) experiments with consecutive bacterial artificial chromosome (BAC) clones to map the breakpoints of the inversion of chromosome 3 which was detected during the karyotypic analysis of the propositus. Homozygous R448C mutations were detected in 2 individuals with 11 β-hydroxylase deficiency. Interestingly, karyotypic change of pericentric inversion [inv(3)(p13q24)] was detected in both individuals who are cousins, one transmitted paternally and the other maternally. The breakpoint at 3p included one interesting gene PPP4R2. Here we present the data of two Turkish families’ members having 11 β-hydroxylase deficiency coupled with the familial chromosomal aberration of inv(3)(p13q24). Our data suggest that codon 448, which is a mutational hot spot in CYP11B1 causing 11 β-hydroxylase deficiency, is not restricted to Jews of Moroccan origin. Phenotypic variations observed in former studies in patients homozygous for R448H were stated to be due to other factors outside the CYP11B1 locus. The breakpoint in 3p might be a candidate region affecting variations in phenotypes of 11 β-hydroxylase deficiency.