TY - JOUR

T1 - Characteristics of the Danish families with multiple endocrine neoplasia type 1

AU - Jäger, Anne Charlotte

AU - Friis-Hansen, Lennart

AU - Hansen, Thomas v.O.

AU - Eskildsen, Peter C.

AU - Sølling, Karsten

AU - Knigge, Ulrich

AU - Hansen, Carsten P.

AU - Andersen, Per H.

AU - Brixen, Kim

AU - Feldt-Rasmussen, Ulla

AU - Kroustrup, Jens Peter

AU - Mollerup, Charlotte L.

AU - Rehfeld, Jens F.

AU - Blichert-Toft, Mogens

AU - Nielsen, Finn C.

N1 - Funding Information: We acknowledge Heidi Lykke Pedersen, Vibeke Trandbohus and Inge Hornung for excellent technical assistance and Ruth Frikke-Schmidt for kind help in calculating haplotypes. We also thank Sten Vadstrup, Dept. of Endocrinology, Nykøbing Falster Hospital, Nykøbing Falster, Denmark; Svante Jansson, Dept. of Endocrinology, Sahlgrenska Hospital, Gottenburg, Sweden; Aage Prange, Dept. of Internal Medicine, Vejle Sygehus, Vejle, Denmark, for supplying patients and clinical data. This work was supported by grants from the Boel Foundation, the Toyota Foundation, the Novo Nordisk Foundation and the Danish Medical Research Council.

PY - 2006/4/25

Y1 - 2006/4/25

N2 - Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier reported mutation. The mutations were predominantly found in exons 9 and 10 encoding the C-terminal part of menin. Seven of the mutations were missense mutations, changing conserved residues. Furthermore screening of 93 out of 153 consecutive patients with primary hyperparathyroidism (pHPT) identified five mutation carriers. Two of these belonged to known MEN1 families, whereas the only MEN1-related disease in the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut endocrine tumours revealed five mutation carries out of 28 patients with sporadic gastrinomas, whereas no mutations were found in 68 patients with other fore-/midgut endocrine tumours. Moreover, screening of 60 consecutive patients with primary prolactinoma did not identify any mutation carriers. Our data indicate that MEN1 mutation screening is efficient in patients with familial MEN1. Screening should also be offered to patients with pHPT or gastrinomas after thorough investigation into the family history. In contrast, sporadic carcinoid tumours or primary prolactinomas are rarely associated with germ-line MEN1 mutations.

AB - Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier reported mutation. The mutations were predominantly found in exons 9 and 10 encoding the C-terminal part of menin. Seven of the mutations were missense mutations, changing conserved residues. Furthermore screening of 93 out of 153 consecutive patients with primary hyperparathyroidism (pHPT) identified five mutation carriers. Two of these belonged to known MEN1 families, whereas the only MEN1-related disease in the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut endocrine tumours revealed five mutation carries out of 28 patients with sporadic gastrinomas, whereas no mutations were found in 68 patients with other fore-/midgut endocrine tumours. Moreover, screening of 60 consecutive patients with primary prolactinoma did not identify any mutation carriers. Our data indicate that MEN1 mutation screening is efficient in patients with familial MEN1. Screening should also be offered to patients with pHPT or gastrinomas after thorough investigation into the family history. In contrast, sporadic carcinoid tumours or primary prolactinomas are rarely associated with germ-line MEN1 mutations.

KW - Carcinoid tumour

KW - Gastrinoma

KW - Menin

KW - Multiple endocrine neoplasia type 1

KW - Mutation

KW - Polymorphism

KW - Primary hyperparathyroidism

KW - Prolactinoma

UR - http://www.scopus.com/inward/record.url?scp=33645850422&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2006.02.008

DO - 10.1016/j.mce.2006.02.008

M3 - Journal article

C2 - 16563611

AN - SCOPUS:33645850422

VL - 249

SP - 123

EP - 132

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

IS - 1-2

ER -