Evidence for a Founder Effect ofSDHBExon 1 Deletion in Brazilian Patients With Paraganglioma
| Autor: | Gustavo F C Fagundes, Felipe Freitas-Castro, Lucas S Santana, Ana Caroline F Afonso, Janaina Petenuci, Mariana F A Funari, Augusto G Guimaraes, Felipe L Ledesma, Maria Adelaide A Pereira, Carolina R Victor, Marcela S M Ferrari, Fernando M A Coelho, Victor Srougi, Fabio Y Tanno, Jose L Chambo, Ana Claudia Latronico, Berenice B Mendonca, Maria Candida B V Fragoso, Ana O Hoff, Madson Q Almeida |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. |
| ISSN: | 1945-7197 0021-972X |
| Popis: | ContextLimited 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.ObjectiveOur aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs.MethodsGenetic 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.ResultsAmong 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 (X2 = 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.ConclusionThe 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. |
| Databáze: | OpenAIRE |
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