| Full text | |
| Author(s): |
da Silva-Grecco, Roseane Lopes
[1, 2]
;
Michelatto, Debora de Paula
[1]
;
Lincoln-de-Carvalho, Carolina Rodrigues
[1]
;
Henrique, Pamela Pontes
[1]
;
da Cunha, Heloisa Marcelina
[2]
;
Palandi-de-Mello, Maricilda
[1]
Total Authors: 6
|
| Affiliation: | [1] Univ Estadual Campinas UNICAMP, Ctr Biol Mol Engn Genet CBMEG, Lab Genet Mol Humana, Campinas, SP - Brazil
[2] Univ Fed Triangulo Mineiro, Inst Ciencias Biol Naturais, Dept Patol Genet & Evolucao, Disciplina Genet Humana, BR-38025180 Uberaba, MG - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | MOLECULAR GENETICS AND METABOLISM REPORTS; v. 5, p. 98-102, DEC 2015. |
| Web of Science Citations: | 0 |
| Abstract | |
Congenital adrenal hyperplasia, one of the most frequent autosome recessive disorders, is caused by defects in steroidogenic enzymes involved in the cortisol biosynthesis. Approximately 95% of the cases are caused by abnormal function of the 21-hydroxylase enzyme. This deficiency leads to androgen excess, consequently, to virilization and rapid somatic growth with accelerated skeletal maturation. Mutations in CYP21A2 are responsible for different forms of 21-hydroxylase deficiency. Mild impairment in the enzymatic activity causes the non-classic or late-onset congenital adrenal hyperplasia that is observed with a prevalence of 1 in 1000 subjects in different populations. The present paper describes a de novo mutation that occurred in the paternal meiosis. The child, who was conceived by in vitro fertilization, presented with precocious puberty and diagnosed with non-classical 21-hydroxylase deficiency. DNA sequencing showed the compound heterozygosis for a de novo CYP21A1P/A2 chimeric gene and the p.Val281Leu mutation inherited from her mother, who was heterozygous for the mutation. The chimeric gene showed pseudogene-derived sequence from 5'-end to intron 3 and CYP21A2 sequences from intron 3 to 3'-end of the gene. Sequencing analysis of the father did not show any mutation. The multiplex ligation-dependent probe amplification (MLPA) assay did not indicate loss of DNA discarding gene deletion but confirmed the chimeric gene. In addition, supernumerary copies of CYP21A1P were observed for both parents and for the affect child. Since paternity has been confirmed, those results suggest that a de novo large gene conversion in the paternal meiosis could have occurred by misalignment of alleles bearing different copy numbers of genes in CYP21 locus. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (AU) | |
| FAPESP's process: | 12/16815-0 - Analysis of alterations in the gene expression and in the enzymatic activity resulting from CYP21A2 gene intronic and exonic variations |
| Grantee: | Débora de Paula Michelatto |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |