Molecular analysis of the Von Hippel-Lindau (VHL) gene in a family with non-syndromic pheochromocytoma: the importance of genetic testing
| Autor: | Sueli A. Clara, Sandro José Conde, Juliana B. Cruz, Denise Perone, Peter Kopp, Célia Regina Nogueira, Leonardo Parr dos Santos Fernandes |
|---|---|
| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Northwestern University (NU) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Oncology
Proband Male Von Hippel-Lindau disease medicine.medical_specialty Pathology von Hippel-Lindau Disease Genetic testing endocrine system diseases Adolescent Doença de Von Hippel-Lindau Endocrinology Diabetes and Metabolism Adrenal Gland Neoplasms Mutation Missense Pheochromocytoma Asymptomatic Polymerase Chain Reaction Germline mutation Pre-Eclampsia Pregnancy Internal medicine medicine Humans Von Hippel–Lindau disease Child Germ-Line Mutation Mutação medicine.diagnostic_test Base Sequence business.industry General Medicine Metanephrines medicine.disease Pedigree Feocromocitoma Von Hippel-Lindau Tumor Suppressor Protein Mutation (genetic algorithm) Mutation Female medicine.symptom business Teste genético |
| Zdroj: | Arquivos Brasileiros de Endocrinologia & Metabologia, Volume: 51, Issue: 9, Pages: 1463-1467, Published: DEC 2007 Arquivos Brasileiros de Endocrinologia & Metabologia v.51 n.9 2007 Arquivos Brasileiros de Endocrinologia & Metabologia Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) instacron:SBEM SciELO Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 0004-2730 |
| Popis: | Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:59:49Z No. of bitstreams: 1 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) Made available in DSpace on 2013-08-22T18:59:49Z (GMT). No. of bitstreams: 1 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) Previous issue date: 2007-12-01 Made available in DSpace on 2013-09-30T19:57:11Z (GMT). No. of bitstreams: 2 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) S0004-27302007000900008.pdf.txt: 19752 bytes, checksum: 6789083165b81218f2b3db6d2e17f82b (MD5) Previous issue date: 2007-12-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:14:51Z No. of bitstreams: 2 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) S0004-27302007000900008.pdf.txt: 19752 bytes, checksum: 6789083165b81218f2b3db6d2e17f82b (MD5) Made available in DSpace on 2014-05-20T15:14:51Z (GMT). No. of bitstreams: 2 S0004-27302007000900008.pdf: 96437 bytes, checksum: 5c4bdd1d5d17b3cd7e07afe6bdf9f76e (MD5) S0004-27302007000900008.pdf.txt: 19752 bytes, checksum: 6789083165b81218f2b3db6d2e17f82b (MD5) Previous issue date: 2007-12-01 Dois pacientes índices da família analisada neste estudo foram submetidos a adrenalectomia bilateral devido a feocromocitoma. Foi, então, realizado o estudo genético dos pacientes e de sete parentes de primeiro grau. Os dois pacientes com feocromocitoma e dois outros membros assintomáticos da família apresentaram a mutação c496G>T no exon 3 do gene VHL. A família perdeu seguimento médico. Três anos após a realização da avaliação genética, a irmã dos pacientes, portadora da mutação, foi encaminhada para o nosso serviço após uma gestação complicada por pré-eclampsia. Ela referia paroxismos sugestivos de feocromocitoma, mas as metanefrinas urinárias eram negativas. Entretanto, a tomografia computadorizada de abdômen evidenciou uma massa adrenal que também se contrastou na cintilografia com metaiodobenzilguanidina (MIBG). Esse estudo mostra que a análise molecular do paciente índice pode levar à identificação de parentes assintomáticos portadores da mutação. Além disso, mesmo com as metanefrinas urinárias negativas, a identificação de uma mutação específica levou a um aumento da suspeita e detecção de feocromocitoma na irmã dos afetados pela doença. The two index patients of the family analyzed in this study had undergone bilateral adrenalectomy for pheochromocytomas. This prompted genetic analyses of the probands and seven first-degree relatives. The two pheochromocytoma patients and two additional asymptomatic family members were found to harbor a mutation c496G>T in exon 3 of the VHL gene. The family was then lost to systematic follow-up. Three years after performing the initial genetic evaluation, the sister of the probands, who was known to carry the same VHL germline mutation, was referred to our service after a pregnancy that was complicated by preeclampsia. She reported paroxysms suggestive for pheochromocytoma, but her urinary metanephrines were negative. However, computerized tomography of the abdomen showed an adrenal mass that was also positive on metaiodobenzylguanidine (MIBG) scintigraphy. This study illustrates that molecular analysis of the index patient(s) can lead to the identification of presymptomatic relatives carrying the mutation. Moreover, despite negative urinary metanephrines, the identification of a specific mutation has led to an increased suspicion and detection of a pheochromocytoma in the sister of the probands. Universidade Estadual Paulista Faculdade de Medicina Departamento de Clínica Médica Northwestern University Division of Endocrinology, Metabolism, and Molecular Medicine Universidade Estadual Paulista Faculdade de Medicina Departamento de Clínica Médica |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|