Consequences of Direct Genetic Testing for Germline Mutations in the Clinical Management of Families With Multiple Endocrine Neoplasia, Type II

作者：Hartmut P.H. Neumann · 发表于：JAMA · 年份：1995 · DOI：10.1001/jama.1995.03530140061033 · 被引用次数：100 · 研究领域：Cancer, Hypoxia, and Metabolism、Adrenal and Paraganglionic Tumors、Thyroid Cancer Diagnosis and Treatment

OBJECTIVE: Multiple endocrine neoplasia, type II (MEN-II) is an autosomal dominant disorder characterized by tumors of thyroid C cells and pheochromocytoma. Recently, germline mutations in the RET proto-oncogene have been identified in patients with MEN-II. The aims of this study were (1) to define the mutations in clinically diagnosed MEN-II families, (2) to compare the results of genetic and biochemical testing, and (3) to evaluate the impact of mutation analyses for the members of these families. DESIGN: Register-based survey study of clinically affected and unaffected members of MEN-II families. SETTING: Register of families from Germany and Spain with pheochromocytomas. Two research laboratories at Cambridge University in the United Kingdom. PATIENTS: We investigated consenting affected and unaffected members belonging to a series of 10 families who met the clinical criteria for MEN-II. MAIN OUTCOME MEASURES: (1) Presence or absence of germline mutation in the RET proto-oncogene in affected and unaffected members of the 10 families, and (2) in the absence of RET mutation in a given family, presence or absence of germline mutation in the von Hippel-Lindau (VHL) gene, which is the susceptibility gene involved in a closely related syndrome, von Hippel-Lindau disease. RESULTS: In eight of these families, RET mutations were identified. The specific mutations were detected in all affected members. The remaining two families without RET mutations were subsequently shown to have...