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Founder effect in multiple endocrine neoplasia type 1 (MEN 1) in Finland
  1. S KYTÖLÄ*,
  3. T EBELING§,
  4. B NORD*,
  5. C LARSSON*,
  6. A HÖÖG,
  7. F K WONG*,
  9. O VIERIMAA**,
  10. B T TEH*,164,
  11. P I SALMELA§,
  12. J LEISTI**
  1. *Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
  2. †Laboratory of Cancer Genetics, Institute of Medical Technology, FIN-33 014 University of Tampere and Tampere University Hospital, Tampere, Finland
  3. ‡Department of Oncology-Pathology, Karolinska Hospital, Stockholm, Sweden
  4. §Department of Internal Medicine, Oulu University Hospital, Oulu, Finland
  5. ¶Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland
  6. **Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland
  7. 164Van Andel Research Institute, Grand Rapids, Michigan, USA
  1. Dr Kytölä, Soili.Kytola{at}

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Editor—Multiple endocrine neoplasia type 1 (MEN 1, OMIM 131100) is transmitted as an autosomal dominant trait with an equal sex distribution and close to full penetrance. Hyperparathyroidism occurs in over 90% of the cases and is invariably associated with multiglandular disease. In addition, the patients may develop tumours of the endocrine pancreas, the anterior pituitary, and the adrenal cortex, as well as lipomas and carcinoids.1The MEN1 tumour suppressor gene at 11q13 was cloned by positional cloning and the protein, menin, has been found to bind specifically to JunD leading to inhibition of JunD activated transcription.2-5 Following the initial description of the disease gene, over 200 MEN1 germline mutations scattered throughout the entire gene have been reported. The majority of these mutations are unique and no clear cut genotype-phenotype correlation has been established so far.3 4 6-13 To date, only a few reports of a founder effect in MEN 1 families have been published.10 14 15 In all the cases, the evidence for a founder chromosome was based on the presence of a shared disease haplotype and aMEN1 mutation, in combination with a common geographical origin of the families involved.

To date, more than 30 rare single gene diseases, mostly autosomal recessive, have been identified in the Finnish population.16 17 The clustering of mutations in the Finnish population can be explained by the mechanisms of isolation, genetic drift, and founder effect. The relatively small founder population, the geographical isolation, and the internal migration movement in the 1500s led to the formation of numerous founder populations. The Finnish population has been widely used in linkage disequilibrium studies for mapping disease gene loci. By combining genetic and clinical investigations with careful genealogical studies, several founder chromosomes for various genetic diseases have been established.17-19 …

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