Author/Editor		Neumann, Hartmut PH; Eng, Charis; Mulligan, Lois M; Glavač, Damjan; Zaeuner, Ingeborg; Ponder, Bruce A J; Crossey, Paul A; Maher, Eamonn R; Brauch, Hiltrud
Title		Consequences of direct genetic testing for germline mutations in the clinical management of families with multiple endocrine neoplasia, type II
Type		članek
Source		JAMA
Vol. and No.		Letnik 274, št. 14
Publication year		1995
Volume		str. 1149-51
Language		eng
Abstract		Objective.-Multiple endocrine neoplasia, type II (MEN-II) is an autosomal dominant disorder characterized by tumors thyroid C cells and pheochromocytoma. Recently, germline mutations in the RET proto-oncogene have been identified in patients with MEN-II. The aims of the 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 a mutation within the VHL gene. The VHL mutations were identified in both families and represent a previosly undescribed base change. After identification of the mutation, premorbid genetic testing was performed in all MEN-II and VHL families, resulting in detection of asymptomatic carriers in the MEN-II families by the presence of a C-cell tumor in only one individual from each family and extra-adrenal pheochromocytoma in three of nine affected individuals in the two families combined.(trunc.)
Descriptors		MULTIPLE ENDOCRINE NEOPLASIA GERM-LINE MUTATION ADOLESCENCE ADULT MIDDLE AGE AGED CHILD, PRESCHOOL CHILD POLYMERASE CHAIN REACTION PROTO-ONCOGENES