Criteria for mutation analysis in MEN 1-suspected patients: MEN 1 case-finding.
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal, dominantly inherited cancer syndrome, with tumours in various endocrine glands. In 1997 the responsible tumour suppressor gene was identified. MEN1 gene germ-line mutations are detected in the vast majority of MEN 1 patients, however, with regard to case-finding, unfortunately only at a very low frequency in patients with apparently sporadic MEN 1-related tumours. In order to increase the detection rate of disease gene carriers among patients with apparently sporadic MEN 1-related tumours, clinical criteria were needed.


RESULTS
In this study MEN1 gene germ-line mutations were revealed in 16/16 MEN 1 patients/families (100%). Based on our clinical experience with MEN 1 patients/families we formulated clinical criteria to identify disease gene carriers among patients with apparently sporadic MEN 1-related tumours. The criteria for MEN 1-suspected patients are: young age at onset (< 35 years) and/or multiple MEN 1-related lesions in a single organ or two distinct organs affected. Application of these criteria yielded MEN1 gene germ-line mutations in nine of 15 MEN 1-suspected patients (60%), thus identifying novel MEN 1 families. Follow up was also guaranteed for patients not fulfilling these criteria.


CONCLUSIONS
The clinical criteria for MEN 1-suspected patients increase the detection rate of germ-line MEN1 gene mutations among patients with apparently sporadic MEN 1-related tumours. These criteria may be used for (presymptomatic) identification of MEN 1 disease gene-carriers, thus enabling early detection of tumour development and timely treatment, as well as genetic counselling.
Roijers
J F
JF
University Medical Center Utrecht, The Netherlands.
de Wit
M J
MJ
van der Luijt
R B
RB
Ploos van Amstel
H K
HK
Höppener
J W
JW
Lips
C J
CJ
D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000302:isolation & purification; D005091:Exons; D005192:Family Health; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000175:diagnosis* / Q000235:genetics*; D012334:RNA, Neoplasm / Q000302:isolation & purification
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm