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SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma
Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. More than 30% of patients with PPGL have a hereditary predisposition. To date, at least 14 tumor susceptibility genes have been described. Mutations in the succinate dehydrogenase comple...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Endocrine Society
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552258/ http://dx.doi.org/10.1210/js.2019-SAT-320 |
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author | Petenuci, Janaina Pereira, Maria Adelaide Zerbini, Maria Cláudia Yamauchi, Fernando Srougi, Victor Tanno, Fabio Chambo, Jose Luis Latronico, Ana Claudia Mendonca, Berenice Fragoso, Maria Almeida, Madson |
author_facet | Petenuci, Janaina Pereira, Maria Adelaide Zerbini, Maria Cláudia Yamauchi, Fernando Srougi, Victor Tanno, Fabio Chambo, Jose Luis Latronico, Ana Claudia Mendonca, Berenice Fragoso, Maria Almeida, Madson |
author_sort | Petenuci, Janaina |
collection | PubMed |
description | Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. More than 30% of patients with PPGL have a hereditary predisposition. To date, at least 14 tumor susceptibility genes have been described. Mutations in the succinate dehydrogenase complex iron sulfur subunit B gene (SDHB) are more associated with paragangliomas and metastatic disease. Patients who are young, with larger tumors (>6 cm), positive genetic testing (especially SDHB) or paraganglioma have a higher risk of metastasis development. Case Report: A 14-yr-old boy was referred to investigate severe hypertension and paroxysmal headache, pallor and tachycardia. Biochemical testing for catecholamine-secreting PPGLs showed: 24h urine metanephrines 1.9 µg (normal range, 0.05 to 1.2), plasma normetanephrine 13.3 nmol/L (<0.9 nmol/L), plasma metanephrine <0.2 nmol/L (<0.5 nmol/L), 24h urine norepinephrine 987 µg (14 to 80), 24h urine epinephrine 0 (0.5 to 20 µg) and 24h urine dopamine 391 µg (65 to 400). Magnetic resonance imaging (MRI) revealed a 6.5 cm heterogenous and high-vascular mass in right adrenal gland topography. A strong positive uptake was evidenced in the metaiodobenzylguanidine (MIBG) scintigraphy. A selective α(1)-receptor blocker (prazosin) was started to control blood pressure and adrenergic symptoms. The patient underwent laparoscopic surgery and anatomopathological analysis revealed a 5.5 cm paraganglioma (PASS criteria= 3). The normal right adrenal gland was identified in the histopathology and there was no continuity between normal adrenal gland and neoplasia. After one year of follow-up, the patient is in complete remission. Genetic analysis by Sanger automated sequencing revealed no pathogenic variants in VHL and SDHD genes. We identified a heterozygous germline synonymous variant c.540 G>A (p.L180=), involving a G>A transition in the last nucleotide of SDHB exon 5. This synonymous variant results in alternative splicing of the SDHB primary transcript. This germline variant was previously reported in a 12-yr-old patient with isolated jugulotympanic paraganglioma, but it has not been associated with catecolamine-secreting paraganglioma. Neck MRI revealed no abnormalities in our patient. Conclusion: We report here a synonymous pathogenic variant in SDHB exon 5 associated with an abdominal functioning paraganglioma. Annual screening for multifocal disease (abdominal and neck PPGLs) and malignancy should be performed. |
format | Online Article Text |
id | pubmed-6552258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-65522582019-06-13 SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma Petenuci, Janaina Pereira, Maria Adelaide Zerbini, Maria Cláudia Yamauchi, Fernando Srougi, Victor Tanno, Fabio Chambo, Jose Luis Latronico, Ana Claudia Mendonca, Berenice Fragoso, Maria Almeida, Madson J Endocr Soc Tumor Biology Background: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. More than 30% of patients with PPGL have a hereditary predisposition. To date, at least 14 tumor susceptibility genes have been described. Mutations in the succinate dehydrogenase complex iron sulfur subunit B gene (SDHB) are more associated with paragangliomas and metastatic disease. Patients who are young, with larger tumors (>6 cm), positive genetic testing (especially SDHB) or paraganglioma have a higher risk of metastasis development. Case Report: A 14-yr-old boy was referred to investigate severe hypertension and paroxysmal headache, pallor and tachycardia. Biochemical testing for catecholamine-secreting PPGLs showed: 24h urine metanephrines 1.9 µg (normal range, 0.05 to 1.2), plasma normetanephrine 13.3 nmol/L (<0.9 nmol/L), plasma metanephrine <0.2 nmol/L (<0.5 nmol/L), 24h urine norepinephrine 987 µg (14 to 80), 24h urine epinephrine 0 (0.5 to 20 µg) and 24h urine dopamine 391 µg (65 to 400). Magnetic resonance imaging (MRI) revealed a 6.5 cm heterogenous and high-vascular mass in right adrenal gland topography. A strong positive uptake was evidenced in the metaiodobenzylguanidine (MIBG) scintigraphy. A selective α(1)-receptor blocker (prazosin) was started to control blood pressure and adrenergic symptoms. The patient underwent laparoscopic surgery and anatomopathological analysis revealed a 5.5 cm paraganglioma (PASS criteria= 3). The normal right adrenal gland was identified in the histopathology and there was no continuity between normal adrenal gland and neoplasia. After one year of follow-up, the patient is in complete remission. Genetic analysis by Sanger automated sequencing revealed no pathogenic variants in VHL and SDHD genes. We identified a heterozygous germline synonymous variant c.540 G>A (p.L180=), involving a G>A transition in the last nucleotide of SDHB exon 5. This synonymous variant results in alternative splicing of the SDHB primary transcript. This germline variant was previously reported in a 12-yr-old patient with isolated jugulotympanic paraganglioma, but it has not been associated with catecolamine-secreting paraganglioma. Neck MRI revealed no abnormalities in our patient. Conclusion: We report here a synonymous pathogenic variant in SDHB exon 5 associated with an abdominal functioning paraganglioma. Annual screening for multifocal disease (abdominal and neck PPGLs) and malignancy should be performed. Endocrine Society 2019-04-30 /pmc/articles/PMC6552258/ http://dx.doi.org/10.1210/js.2019-SAT-320 Text en Copyright © 2019 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Tumor Biology Petenuci, Janaina Pereira, Maria Adelaide Zerbini, Maria Cláudia Yamauchi, Fernando Srougi, Victor Tanno, Fabio Chambo, Jose Luis Latronico, Ana Claudia Mendonca, Berenice Fragoso, Maria Almeida, Madson SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma |
title | SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma |
title_full | SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma |
title_fullStr | SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma |
title_full_unstemmed | SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma |
title_short | SAT-320 A Synonymous Pathogenic Variant (p.l180=) in SDHB Gene Identified in a Young Patient with Abdominal Paraganglioma |
title_sort | sat-320 a synonymous pathogenic variant (p.l180=) in sdhb gene identified in a young patient with abdominal paraganglioma |
topic | Tumor Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552258/ http://dx.doi.org/10.1210/js.2019-SAT-320 |
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