Novel Deletion Alleles Carrying Cyp21a1p/a2 Chimeric Genes In Brazilian Patients With 21-hydroxylase Deficiency.

dc.creatorCoeli, Fernanda B
dc.creatorSoardi, Fernanda C
dc.creatorBernardi, Renan D
dc.creatorde Araújo, Marcela
dc.creatorPaulino, Luciana C
dc.creatorLau, Ivy F
dc.creatorPetroli, Reginaldo J
dc.creatorde Lemos-Marini, Sofia H V
dc.creatorBaptista, Maria T M
dc.creatorGuerra-Júnior, Gil
dc.creatorde-Mello, Maricilda P
dc.date2010
dc.date2015-11-27T13:18:00Z
dc.date2015-11-27T13:18:00Z
dc.date.accessioned2018-03-29T01:11:09Z
dc.date.available2018-03-29T01:11:09Z
dc.identifierBmc Medical Genetics. v. 11, p. 104, 2010.
dc.identifier1471-2350
dc.identifier10.1186/1471-2350-11-104
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/20587039
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/198922
dc.identifier20587039
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1299155
dc.descriptionCongenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in CYP21A2 gene. The human gene is located at 6p21.3 within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module. The CYP21 extra copy is a pseudogene (CYP21A1P). In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric CYP21A1P/A2 genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular C4/CYP21 locus. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency. We used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of CYP21A1P/A2 chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with C4/CYP21 30-kb deletion were included in the study. An allele carrying a CYP21A1P/A2 chimeric gene was found unusually associated to a C4B/C4A Taq I 6.4-kb fragment, generally associated to C4B and CYP21A1P deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in CYP21A1P of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different approaches revealed nine haplotypes for deleted 21-hydroxylase deficiency alleles. This study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying CYP21A1P/A2 chimeric genes in Brazil.
dc.description11
dc.description104
dc.languageeng
dc.relationBmc Medical Genetics
dc.relationBMC Med. Genet.
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAdrenal Hyperplasia, Congenital
dc.subjectAlleles
dc.subjectBlotting, Southern
dc.subjectBrazil
dc.subjectExons
dc.subjectGene Amplification
dc.subjectGene Deletion
dc.subjectGenes, Recessive
dc.subjectHumans
dc.subjectMutant Chimeric Proteins
dc.subjectNucleic Acid Hybridization
dc.subjectPolymerase Chain Reaction
dc.subjectPseudogenes
dc.subjectSequence Deletion
dc.subjectSteroid 21-hydroxylase
dc.titleNovel Deletion Alleles Carrying Cyp21a1p/a2 Chimeric Genes In Brazilian Patients With 21-hydroxylase Deficiency.
dc.typeArtículos de revistas


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