Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile

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Lourenco, Jr., D. M. ^[1] ; Toledo, R. A. ^[1] ; Mackowiak, I. I. ^[1] ; Coutinho, F. L. ^[1] ; Cavalcanti, M. G. ^[1] ; Correia-Deur, J. E. M. ^[1] ; Montenegro, F. ^[2] ; Siqueira, S. A. C. ^[3] ; Margarido, L. C. ^[4] ; Machado, M. C. ^[5] ; Toledo, S. P. A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, LIM 25, Unidade Endocrinol Genet, BR-01246903 Sao Paulo - Brazil

^[2] FMUSP, Dept Cirurgia Cabeca & Pescoco, Sao Paulo - Brazil

^[3] FMUSP, Dept Patol Cirurgica, Sao Paulo - Brazil

^[4] FMUSP, Dept Dermatol, Sao Paulo - Brazil

^[5] FMUSP, Dept Cirugia Geral, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF ENDOCRINOLOGY; v. 159, n. 3, p. 259-274, SEP 2008.
• Citações Web of Science: 37

Resumo

Objective: Only few large families with multiple endocrine neoplasia type 1 (MEN1) have been documented. Here, we aimed to investigate the clinical features of a seven-generation Brazilian pedigree. which included 715 at-risk family members. Design: Genealogical and geographic analysis was used to identify the MEN1 pedigree. Clinical and genetic approach was applied to characterize the phenotypic and genotypic features of the family members. Results: Our genetic data indicated that a founding mutation in the MEN1 gene has occurred in this extended Brazilian family. Fifty family members were diagnosed with MEN1. Very high frequencies of functioning and non-functioning MEN1-related tumors were documented and the prevalence of prolactinoma (29.6%) was similar to that previously described in prolactinoma-variant Burin (32%). In addition, bone mineral density analysis revealed severe osteoporosis (T,-2.87 +/- 0.32) of compact bone (distal radius) in hyperparathyroidism (HPT)/MEN1 patients. while marked bone mineral loss in the lumbar spine (T,-1.95 +/- 0.39). with most cancellous bone, and femoral neck (mixed composition: T,-1.48 +/- 0.27) were also present. Conclusions: In this study, we described clinically and genetically the fifth largest MEN1 family in the literature. Our data confirm previous findings suggesting that prevalence of MEN1-related tumors in large families may differ from reports combining cumulative data of small families. Furthermore. we were able to evaluate the bone status in HPT/MEN1 cases, a subject that has been incompletely approached in the literature. We discussed the bone loss pattern found in our MEN1 patients comparing with that of patients with sporadic primary HPT. (AU)

• Processo FAPESP: 02/09860-8 - Neoplasia endócrina múltipla tipo 1: análise de massa óssea, estudos de perda de heterozigosidade em tumores cutâneos, caracterização de mutação gênica e rastreamento gênico de famílias brasileiras
• Beneficiário: Sergio Pereira de Almeida Toledo
• Modalidade de apoio: Auxílio à Pesquisa - Regular