| Texto completo | |
| Autor(es): Mostrar menos - |
Gomes, Nathalia Lisboa
;
Batista, Rafael Loch
;
Nishi, Mirian Y.
;
Lerario, Antonio Marcondes
;
Silva, Thatiana E.
;
Narcizo, Amanda de Moraes
;
Figueredo Benedetti, Anna Flavia
;
de Assis Funari, Mariana Ferreira
;
Faria Junior, Jose Antonio
;
Moraes, Daniela Rodrigues
;
Lousada Quintao, Lia Mesquita
;
Montenegro, Luciana Ribeiro
;
Martins Ferrari, Maria Teresa
;
Jorge, Alexander A.
;
Arnhold, Ivo J. P.
;
Costa, Elaine Maria Frade
;
Domenice, Sorahia
;
Mendonca, Berenice Bilharinho
Número total de Autores: 18
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 107, n. 5, p. 10-pg., 2022-02-03. |
| Resumo | |
Context Massively parallel sequencing (MPS) technologies have emerged as a first-tier approach for diagnosing several pediatric genetic syndromes. However, MPS has not been systematically integrated into the diagnostic workflow along with clinical/biochemical data for diagnosing 46,XY differences of sex development (DSD). Objective To analyze the contribution of phenotypic classification either alone or in association with genetic evaluations, mainly MPS, for diagnosing a large cohort of 46,XY DSD patients. Design/patients 209 nonsyndromic 46,XY DSD index cases from a Brazilian DSD center were included. Patients were initially classified into 3 subgroups according to clinical and biochemical data: gonadal dysgenesis (GD), disorders of androgen secretion/action, and DSD of unknown etiology. Molecular genetic studies were performed by Sanger sequencing and/or MPS. Results Clinical/biochemical classification into either GD or disorders of hormone secretion/action was obtained in 68.4% of the index cases. Among these, a molecular diagnosis was obtained in 36% and 96.5%, respectively. For the remainder 31.6% classified as DSD of clinically unknown etiology, a molecular diagnosis was achieved in 31.8%. Overall, the molecular diagnosis was achieved in 59.3% of the cohort. The combination of clinical/biochemical and molecular approaches diagnosed 78.9% of the patients. Clinical/biochemical classification matched with the genetic diagnosis in all except 1 case. DHX37 and NR5A1 variants were the most frequent genetic causes among patients with GD and DSD of clinical unknown etiology, respectively. Conclusions The combination of clinical/biochemical with genetic approaches significantly improved the diagnosis of 46,XY DSD. MPS potentially decreases the complexity of the diagnostic workup as a first-line approach for diagnosing 46,XY DSD. (AU) | |
| Processo FAPESP: | 13/02162-8 - Patogênese molecular e caracterização de doenças monogênicas do desenvolvimento: um caminho para a medicina translacional |
| Beneficiário: | Berenice Bilharinho de Mendonça |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 14/50137-5 - Caracterização molecular de doenças monogênicas do desenvolvimento por sequenciamento em larga escala |
| Beneficiário: | Berenice Bilharinho de Mendonça |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |
| Processo FAPESP: | 05/04726-0 - Caracterização molecular das doenças endócrinas congênitas que afetam o crescimento e o desenvolvimento |
| Beneficiário: | Ana Claudia Latronico Xavier |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 10/51102-0 - Pesquisa de mutações nos genes BMP15 e GDF9 em mulheres portadoras de insuficiência ovariana prematura: desenvolvimento de metodologia para estudo funcional das mutações em células humanas de granulosa imorta |
| Beneficiário: | Mariza Augusta Gerdulo dos Santos |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |