| Full text | |
| Author(s): Show less - |
Fagundes, Gustavo F. C.
[1]
;
Petenuci, Janaina
[1]
;
Lourenco Jr, Delmar M.
;
Trarbach, Ericka B.
[2]
;
Pereira, Maria Adelaide A.
[3]
;
Correa D'Eur, Joya Emilie
[2]
;
Hoff, Ana O.
[4]
;
Lerario, Antonio M.
[1]
;
Zerbini, Maria Claudia N.
[5]
;
Siqueira, Sheila
[5]
;
Yamauchi, Fernando
[6]
;
Srougi, Victor
[7]
;
Tanno, Fabio Y.
[7]
;
Chambo, Jose Luis
[7]
;
Latronico, Ana Claudia
[1]
;
Mendonca, Berenice B.
[1]
;
Fragoso, V, Maria Candida B.
;
Almeida, Madson Q.
[8, 9]
Total Authors: 18
|
| Affiliation: | [1] Univ Sao Paulo, Fac Med, Hosp Clin, Serv Endocrinol & Metabol, Unidade Suprarrenal, Lab Hormonios & Genet Mol, LIM 42, BR-05403000 Sao Paulo - Brazil
[2] Lourenco Jr, Jr., Delmar M., Univ Sao Paulo, Fac Med, Hosp Clin, Serv Endocrinol & Metabol, Unidade Endocrinol Gene, LIM 25, BR-05403000 Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Med, Hosp Clin, Serv Endocrinol & Metabol, Unidade Endocrinol Gera, BR-05403000 Sao Paulo - Brazil
[4] Lourenco Jr, Jr., Delmar M., Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Serv Endocrinol, BR-05403000 Sao Paulo - Brazil
[5] Univ Sao Paulo, Fac Med, Hosp Clin, Div Anat Patol, BR-05403000 Sao Paulo - Brazil
[6] Univ Sao Paulo, Fac Med, Hosp Clin, Dept Radiol & Oncol, BR-05403000 Sao Paulo - Brazil
[7] Univ Sao Paulo, Fac Med, Hosp Clin, Serv Urol, BR-05403000 Sao Paulo - Brazil
[8] Fragoso, Maria Candida B., V, Univ Sao Paulo, Fac Med, Hosp Clin, Serv Endocrinol & Metabol, Unidade Suprarrenal, Lab Hormonios & Genet Mol, LIM 42, BR-05403000 Sao Paulo - Brazil
[9] Fragoso, Maria Candida B., V, Lourenco Jr, Jr., Delmar M., Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Serv Endocrinol, BR-05403000 Sao Paulo - Brazil
Total Affiliations: 9
|
| Document type: | Journal article |
| Source: | JOURNAL OF THE ENDOCRINE SOCIETY; v. 3, n. 9, p. 1682-1692, SEP 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
Context: Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years. Objective: Genotype-phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied. Design: We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease. Results: PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-yearold boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations. Conclusion: VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis. Copyright (C) 2019 Endocrine Society (AU) | |
| FAPESP's process: | 15/17049-8 - Genetic investigation of aldosterone-producing adrenocortical tumors by next generation sequencing |
| Grantee: | Madson Queiroz Almeida |
| Support type: | Regular Research Grants |