Mutations distribution and correlation with phenotypes in steroid 21-hydroxylase deficiency Italian patients

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134183

Carrera, P; Volorio, S; Ferran, M ^[1]

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1. and others

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 suggest 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.

• OSTI ID: 134183
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CODONS
CORRELATIONS
DETECTION
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
GENES
GENOTYPE
HEREDITARY DISEASES
HYDROXYLASES
ITALY
METABOLIC DISEASES
MUTATION FREQUENCY
OLIGONUCLEOTIDES
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
RECESSIVE MUTATIONS
SPLICING
STEROIDS