CYP21A2 gene duplication with a severe pathogenic variant is a benign allele that does not confirm clinical suspicions of 21-hydroxylase deficiency

Gomes, Susana; Silva, Júlia; Pereira-Caetano, Iris; Gonçalves, João

http://hdl.handle.net/10400.18/5944

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Authors

Gomes, Susana

Silva, Júlia

Pereira-Caetano, Iris

Gonçalves, João

Abstract(s)

Introduction: Congenital Adrenal Hyperplasia (CAH), one the most common autosomal recessive disorders, is regularly managed during genetic counselling (GC). The coding gene (CYP21A2) for 21-hydroxylase (21-OH), is located (in cis) with its pseudogene (CYP21A1P) in the RCCX cluster (6p21.3) and, the most common structure of this cluster comprises a single copy of each one. However, genotypes associated with CYP21A2 duplications can be detected in individuals during familial and/or pre-conceptional studies. In this duplicated alleles, the severe variant c.955C>T p.(Glu319*) is frequently detected, but is usually present in the proximal CYP21A2 copy. This means, that even in the presence of a severe variant, its allele is not pathogenic. Therefore, the aim of this work is to emphasize the importance of a better strategy of molecular analysis and an accurate interpretation of its results, in order to establish a correct genotyping of family members and partners, and provide a more reliable genetic counselling.