ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2004) 7 P309

Mutation testing in multiple endocrine neoplasia (MEN1): an audit

B Vaidya1, AT Hattersley1 & S Ellard2

1Department of Endocrinology, Royal Devon & Exeter Hospital, Exeter, UK; 2Department of Molecular Genetics, Royal Devon & Exeter Hospital, Exeter, UK.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by various combinations of tumours of the parathyroid, enteropancreatic and anterior pituitary glands. With the identification of the MEN1 gene, the genetic diagnosis of this condition is now possible. In this study, we have examined whether different clinical presentations of MEN1 are more likely to yield positive mutation result.

Methods: We analysed the data on all MEN1 mutation analyses carried out at our diagnostic laboratory during 1997-2003. Mutation analysis was performed by direct DNA sequencing of the coding regions of the MEN1 gene.

Results: During the period, we carried out mutation analysis in 179 probands and 98 family members of the affected cases. Mutations were identified in 64 (36%) probands. These included missense (27%), deletion/insertion (52%), nonsense (16%) and splice site (6%) mutations, which were scattered throughout the coding region. We further analysed 145 probands, in whom the clinical data were complete. Amongst them, mutations were identified in 26/57 (46%) probands with a family history and in 16/88 (18%) sporadic cases. We found mutations in 12/17 (71%) with 3 MEN1-associated tumours, 24/70 (34%) with 2 tumours and 6/58 (10%) with 1 tumour. 4/13 (31%) with familial hyperparathyroidism but none of the 6 with familial pituitary tumours were found to have mutation. Of the 98 family members, we found mutations in 22/84 (26%) tested for prediction and in 13/14 (93%) tested for diagnosis.

Conclusion: The likelihood of identification of MEN1 mutation depends upon the phenotypic characteristics of the individual patient and his/her family.

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