Author/Editor | Dolžan, V; Stopar-Obreza, M; Žerjav-Tanšek, M; Breskvar, K; Kržišnik, C; Battelino, T | |
Title | Mutational spectrum of congenital adrenal hyperplasia in Slovenian patients: a novel Ala15Thr mutation and Pro30Leu within a larger gene conversion associated with a severe form of the disease | |
Type | članek | |
Source | Eur J Endocrinol | |
Vol. and No. | Letnik 149 | |
Publication year | 2003 | |
Volume | str. 137-44 | |
Language | eng | |
Abstract | Objective: To analyse the mutational spectrum, the associated haplotypes and the genotype-phenotype correlation, and to design a reliable and rational approach for CYP21 mutation detection in Slovenian congenital adrenal hyperplasia (CAH) patients. Design: Molecular analysis of the CYP21 gene was performed in 36 CAH patients and 79 family members. Methods: Southern blotting, sequence-specific PCR amplification (PCR-SSP), sequence-specific oligonucleotide hybridisation (PCR-SSO) and sequencing were used to detect CYP21 gene deletions, conversions and point mutations. Results: CYP21 gene deletion was the most frequent mutation (36.4%). Large gene conversions detectable only by Southern blotting represented 12.1%, and gene conversions involving the promoter region represented 7.6% of the mutated alleles. The most frequent point mutations were: intron 2 splice mutation 16.7%, I1e172Asn mutation 7.6%, G1n318Stop 7.5% and Pro30Leu 12.2% of alleles. A correlation between the genotype and the clinical phenotype similar to those described for large populations was observed. The finding of Pro30Leu mutation linked to a gene conversion could explain the simple virilising (SV) phenotype in compound heterozygotes for the Pro30Leu and a severe mutation. In two siblings with a salt wasting form of CAH (SW-CAH), a novel mutation AIa15Thr was found on the allele characterised by Pro30Leu mutation and gene conversion involving the promoter region. Conclusions: Our genotyping approach allowed reliable diagnosis of CAH in the Slovenian population. The high frequency of CYP21 gene aberrations on Pro30Leu positive alleles justified systematic searching for a gene conversion in the promoter region using the PCR-SSP reaction. | |
Descriptors | ADRENAL HYPERPLASIA, CONGENITAL CHILD AGE FACTORS SEX FACTORS ALLELES BLOTTING, SOUTHERN DNA MUTATIONAL ANALYSIS GENE CONVERSION GENE DELETION GENOTYPE HAPLOTYPES OLIGONUCLEOTIDES PHENOTYPE POINT MUTATION POLYMERASE CHAIN REACTION SLOVENIA STEROID HYDROXYLASES |