DHX37 and NR5A1 Variants Identified in Patients with 46,XY Partial Gonadal Dysgenesis

Autor(es)

de Oliveira, Felipe Rodrigues ; Mazzola, Tais Nitsch ; de Mello, Maricilda Palandi ; Francese-Santos, Ana Paula ; de Lemos-Marini, Sofia Helena V. ; Maciel-Guerra, Andrea Trevas ; Hiort, Olaf ; Werner, Ralf ; Guerra-Junior, Gil ; Fabbri-Scallet, Helena

• Tipo de documento: Artigo Científico
• Fonte: LIFE-BASEL; v. 13, n. 5, p. 11-pg., 2023-04-27.

Resumo

The group of disorders known as 46,XY gonadal dysgenesis (GD) is characterized by anomalies in testis determination, including complete and partial GD (PGD) and testicular regression syndrome (TRS). Several genes are known to be involved in sex development pathways, however approximately 50% of all cases remain elusive. Recent studies have identified variants in DHX37, a gene encoding a putative RNA helicase essential in ribosome biogenesis and previously associated with neurodevelopmental disorders, as a cause of PGD and TRS. To investigate the potential role of DHX37 in disorders of sexual development (DSD), 25 individuals with 46,XY DSD were analyzed and putative pathogenic variants were found in four of them. WES analyses were performed on these patients. In DHX37, the variant p.(Arg308Gln), recurrent associated with DSD, was identified in one patient; the p.(Leu467Val), predicted to be deleterious, was found together with an NR5A1 loss-of-function variant in patient 2; and, the p.(Val999Met) was identified in two unrelated patients, one of whom (patient 3) also carried a pathogenic NR5A1 variant. For both patients carrying DHX37 and NR5A1 pathogenic variants, a digenic inheritance is suggested. Our findings support the importance of DHX37 variants as a cause of disorders of sex development, implying a role in testis development. (AU)

• Processo FAPESP: 18/19445-6 - Uso das técnicas de transcriptoma, exoma e expressão gênica para elucidar diferentes fenótipos de distúrbios da diferenciação do sexo em pacientes 46,xy
• Beneficiário: Helena Fabbri Scallet
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/04763-4 - Aplicação da técnica de sequenciamento do exoma para identificar mutações patogênicas na disgenesia gonadal parcial 46,XY
• Beneficiário: Andrea Trevas Maciel Guerra
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/01054-0 - Busca por variantes no gene DHX37 em pacientes com Disgenesia Gonadal Parcial 46,XY e Síndrome de Regressão Testicular
• Beneficiário: Felipe Rodrigues de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica