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| Autor(es): Mostrar menos - |
Fagundes, Gustavo F. C.
;
Freitas-Castro, Felipe
;
Santana, Lucas S.
;
Afonso, Ana Caroline F.
;
Petenuci, Janaina
;
Funari, Mariana F. A.
;
Guimaraes, Augusto G.
;
Ledesma, Felipe L.
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Pereira, Maria Adelaide A.
;
Victor, Carolina R.
;
Ferrari, Marcela S. M.
;
Coelho, Fernando M. A.
;
Srougi, Victor
;
Tanno, Fabio Y.
;
Chambo, Jose L.
;
Latronico, Ana Claudia
;
Mendonca, Berenice B.
;
Fragoso, Maria Candida B., V
;
Hoff, Ana O.
;
Almeida, Madson Q.
Número total de Autores: 20
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| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. N/A, p. 10-pg., 2023-01-18. |
| Resumo | |
Context Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula. Objective Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs. Methods Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint. Results Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X-2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin. Conclusion The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas. (AU) | |
| Processo FAPESP: | 19/15873-6 - Investigação de novos aspectos genéticos, clínicos e anatomopatológicos da hipertensão arterial de origem endócrina |
| Beneficiário: | Madson Queiroz Almeida |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 21/10101-5 - Investigação de novas alterações genética associadas à patogênese dos Aldosteronomas por sequenciamento exômico |
| Beneficiário: | Augusto Garcia Guimarães |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 21/11240-9 - Sequenciamento completo do exoma para investigação de novas causas genéticas dos Feocromocitomas e Paragangliomas metastáticos |
| Beneficiário: | Felipe Freitas de Castro |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 21/10363-0 - Sequenciamento completo do exoma para investigação de novas causas genéticas do Hiperaldosteronismo primário causado por hiperplasia adrenal bilateral |
| Beneficiário: | Lucas Santos de Santana |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |