J Clin Endocrinol Metab
Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brasil.
Published: July 2023
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 (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.
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.
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http://dx.doi.org/10.1210/clinem/dgad028 | DOI Listing |
Exp Ther Med
February 2025
Molecular Pathology, Azienda USL-IRCCS di Reggio Emilia, I-42123 Reggio Emilia, Italy.
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with an annual incidence of ~2 cases per million worldwide. The hereditary form is more likely to present in younger patients. To date, PPGL is considered a complex pathology that is difficult to diagnose.
View Article and Find Full Text PDFEur J Endocrinol
January 2025
Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil.
Objective: Germline and somatic drivers are identified in 30% and 40% of pheochromocytomas and paragangliomas (PPGLs), respectively. In this study, we investigated the genetic landscape of PPGLs in a Brazilian cohort.
Methods: We studied 182 index patients with PPGLs (116 females and 66 males), comprising 118 pheochromocytoma and 70 paraganglioma cases.
Sichuan Da Xue Xue Bao Yi Xue Ban
September 2024
( 610041) Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.
Objective: To investigate the clinicopathological features, immunophenotypes, molecular genetic alterations, and prognosis of succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC).
Methods: A total of 11 cases of SDH-RCC diagnosed at West China Hospital, Sichuan University between 2016 and 2023 were selected for clinicopathological, immunohistochemical, and DNA sequencing analyses.
Results: Among the 11 cases of SDH-RCC, there were 5 male patients and 6 female patients.
Best Pract Res Clin Endocrinol Metab
August 2024
Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil; Unidade de Oncologia Endócrina, Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil. Electronic address:
Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with clinical heterogeneity and a high association with hereditary disease, affecting approximately 30 % of the cases. Differences in the presentation and genetic etiologies of PPGLs have been demonstrated between Chinese and European patients. The frequency of germline genetic diagnosis was remarkably higher in Brazilian patients (∼50 %) compared with other cohorts (Chinese 21 %, European 31 %, and The Cancer Genome Atlas Program cohort 27 %).
View Article and Find Full Text PDFJCEM Case Rep
November 2023
Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM/25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brasil.
Carney-Stratakis syndrome (CSS) is an autosomal dominant rare syndrome, with incomplete penetrance, characterized by the association of paragangliomas and/or pheochromocytomas and gastrointestinal stromal tumors (GISTs). CSS is caused by germline heterozygous loss-of-function pathogenic variants (PVs) in the succinate dehydrogenase subunit genes (), with and being the most frequent. To date, only 2 germline PVs (c.
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