Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase gene (CYP21A2). Most of CYP21A2 mutations result from intergenic recombinations between CYP21A2 and closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for 5-10% of 21-hydroxylase deficiency alleles. Intronic variants represent only a little part of these but their effect on the protein is generally deleterious. The aim of this paper is to provide a comprehensive literary review regarding all intronic CYP21A2 pathological variants reported to date. In addition, we describe three novel causing disease variants in our patients affected by the classic form of CAH: IVS4-1G > A, IVS5-8 T > A, IVS8-2A > G. In silico analysis revealed that all these substitutions affect the splicing process leading to a nonfunctional protein. Based on these results, we are able to classify them as pathological variants according to the patient's phenotype.

Concolino, P., Rizza, R., Costella, A., Carrozza, C., Zuppi, C., Capoluongo, E. D., CYP21A2 intronic variants causing 21-hydroxylase deficiency, <<METABOLISM, CLINICAL AND EXPERIMENTAL>>, 2017; 71 (N/A): 46-51. [doi:10.1016/j.metabol.2017.03.003] [http://hdl.handle.net/10807/108514]

CYP21A2 intronic variants causing 21-hydroxylase deficiency

Rizza, Roberta;Costella, Alessandra;Carrozza, Cinzia;Zuppi, Cecilia;Capoluongo, Ettore Domenico
Ultimo
2017

Abstract

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase gene (CYP21A2). Most of CYP21A2 mutations result from intergenic recombinations between CYP21A2 and closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for 5-10% of 21-hydroxylase deficiency alleles. Intronic variants represent only a little part of these but their effect on the protein is generally deleterious. The aim of this paper is to provide a comprehensive literary review regarding all intronic CYP21A2 pathological variants reported to date. In addition, we describe three novel causing disease variants in our patients affected by the classic form of CAH: IVS4-1G > A, IVS5-8 T > A, IVS8-2A > G. In silico analysis revealed that all these substitutions affect the splicing process leading to a nonfunctional protein. Based on these results, we are able to classify them as pathological variants according to the patient's phenotype.
2017
Inglese
Concolino, P., Rizza, R., Costella, A., Carrozza, C., Zuppi, C., Capoluongo, E. D., CYP21A2 intronic variants causing 21-hydroxylase deficiency, <<METABOLISM, CLINICAL AND EXPERIMENTAL>>, 2017; 71 (N/A): 46-51. [doi:10.1016/j.metabol.2017.03.003] [http://hdl.handle.net/10807/108514]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/108514
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 11
social impact