Background: More than 90% of Congenital Adrenal Hyperplasia (CAH) cases are associated with mutations in the 21-hydroxylase gene (CYP21A2) in the HLA class III area on the short arm of chromosome 6p21.3. In this region, a 30 kb deletion produces a non functional chimeric gene with its 5' and 3' ends corresponding to CYP21A1P pseudogene and CYP21A2, respectively. To date, five different CYP21A1P/CYP21A2 chimeric genes have been found and characterized in recent studies. In this paper, we describe a new CYP21A1P/CYP21A2 chimera (CH-6) found in an Italian CAH patient. Methods: Southern blot analysis and CYP21A2 sequencing were performed on the patient. In addition, in order to isolate the new CH-6 chimeric gene, two different strategies were used. Results: The CYP21A2 sequencing analysis showed that the patient was homozygote for the g. 655C/A > G mutation and heterozygote for the p. P30L missense mutation. In addition, the promoter sequence revealed the presence, in heterozygosis, of 13 SNPs generally produced by microconversion events between gene and pseudogene. Southern blot analysis showed that the woman was heterozygote for the classic 30-kb deletion producing a new CYP21A1P/CYP21A2 chimeric gene (CH-6). The hybrid junction site was located between the end of intron 2 pseudogene, after the g. 656C/A > G mutation, and the beginning of exon 3, before the 8 bp deletion. Consequently, CH-6 carries three mutations: the weak pseudogene promoter region, the p. P30L and the g.655C/A > G splice mutation. Conclusion: We describe a new CYP21A1P/CYP21A2 chimera (CH-6), associated with the HLAB15, DR13 haplotype, in a young Italian CAH patient.

Concolino, P., Mello, E., Minucci, A., Giardina, E., Zuppi, C., Toscano, V., et al. (2009). A new CYP21A1P/CYP21A2 chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form. BMC MEDICAL GENETICS, 10-72 [10.1186/1471-2350-10-72].

A new CYP21A1P/CYP21A2 chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form

GIARDINA, EMILIANO;
2009-01-01

Abstract

Background: More than 90% of Congenital Adrenal Hyperplasia (CAH) cases are associated with mutations in the 21-hydroxylase gene (CYP21A2) in the HLA class III area on the short arm of chromosome 6p21.3. In this region, a 30 kb deletion produces a non functional chimeric gene with its 5' and 3' ends corresponding to CYP21A1P pseudogene and CYP21A2, respectively. To date, five different CYP21A1P/CYP21A2 chimeric genes have been found and characterized in recent studies. In this paper, we describe a new CYP21A1P/CYP21A2 chimera (CH-6) found in an Italian CAH patient. Methods: Southern blot analysis and CYP21A2 sequencing were performed on the patient. In addition, in order to isolate the new CH-6 chimeric gene, two different strategies were used. Results: The CYP21A2 sequencing analysis showed that the patient was homozygote for the g. 655C/A > G mutation and heterozygote for the p. P30L missense mutation. In addition, the promoter sequence revealed the presence, in heterozygosis, of 13 SNPs generally produced by microconversion events between gene and pseudogene. Southern blot analysis showed that the woman was heterozygote for the classic 30-kb deletion producing a new CYP21A1P/CYP21A2 chimeric gene (CH-6). The hybrid junction site was located between the end of intron 2 pseudogene, after the g. 656C/A > G mutation, and the beginning of exon 3, before the 8 bp deletion. Consequently, CH-6 carries three mutations: the weak pseudogene promoter region, the p. P30L and the g.655C/A > G splice mutation. Conclusion: We describe a new CYP21A1P/CYP21A2 chimera (CH-6), associated with the HLAB15, DR13 haplotype, in a young Italian CAH patient.
2009
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/03 - GENETICA MEDICA
English
adenine; cytochrome P450 21A1P; cytochrome P450 21A2; guanine; steroid 21 monooxygenase; unclassified drug; CYP21A2 protein, human; HLA B antigen; HLA B15; HLA DR antigen; HLA DR13; HLA-B15; HLA-DR13; adult; article; case report; chimera; congenital adrenal hyperplasia; exon; female; frameshift mutation; gene deletion; gene identification; gene location; gene sequence; genetic association; haplotype; heterozygosity; homozygosity; human; intron; missense mutation; nucleic acid base substitution; nucleotide sequence; promoter region; pseudogene; single nucleotide polymorphism; Southern blotting; allele; Caucasian; enzymology; genetics; Italy; mutation; polymerase chain reaction; Adrenal Hyperplasia, Congenital; Adult; Alleles; Blotting, Southern; Chimera; DNA Mutational Analysis; European Continental Ancestry Group; Female; Haplotypes; HLA-B Antigens; HLA-DR Antigens; Humans; Introns; Italy; Mutation; Polymerase Chain Reaction; Pseudogenes; Steroid 21-Hydroxylase
Concolino, P., Mello, E., Minucci, A., Giardina, E., Zuppi, C., Toscano, V., et al. (2009). A new CYP21A1P/CYP21A2 chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form. BMC MEDICAL GENETICS, 10-72 [10.1186/1471-2350-10-72].
Concolino, P; Mello, E; Minucci, A; Giardina, E; Zuppi, C; Toscano, V; Capoluongo, E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39507
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