Title: Mutations distribution and correlation with phenotypes in steroid 21-hydroxylase deficiency Italian patients
Abstract: Steroid 21-hydroxylase deficiency is recessively inherited and accounts for over 90% of the genetic disorders of steroidogenesis (CAH). We previously described the distribution of the whole deletion (14.4%) and large scale gene conversion (7.8%) at the P450c21-B locus in our population. In this study we determined the distribution of seven point mutations and searched for new mutations in patients where large rearrangements were not found. For this purpose we have studied 45 Italian families using a P450c21-B-specific PCR in combination with either dot blot analysis and allele-specific oligonucleotide hybridization or by cloning and sequencing. Molecular results have indicated a high frequency of point mutations (61%) corresponding to deleterious sequences normally present in the pseudogene. In particular, only 3 of them were prominent: the splicing mutation at codon 281 (9/16) was the most common within the non-classic form. By cloning and sequencing we detected a deletion of the C2029 residue causing a frameshift and the downstream insertion of a stop codon (2124-2126). This mutation was found in a non-classical patient who is a compound heterozygote for the mutation 281. Family genotyping revealed 5 de novo mutations, and in 8 asymptomatic parents, we detected causative mutations in both alleles. These data suggestmore » that phenotype is not always correlated to allelic variations in P450c21-B genes. For this reason, in these families prenatal diagnosis should be performed by direct detection of mutations instead of linkage analysis.« less
Publication Year: 1994
Publication Date: 1994-09-01
Language: en
Type: article
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