Authors: Gardner, Rebecca J.; Mackay, Deborah J.G.; Mungall, Andrew J.¹; Polychronakos, Constantin²; Siebert, Reiner³; Shield, Julian P.H.⁴; Temple, I. Karen⁵; Robinson, David O.

Source: Human Molecular Genetics, Volume 9, Number 4, 1 March 2000 , pp. 589-596(8)

Publisher: Oxford University Press

Abstract:

Recently, we reported the localization of a gene for transient neonatal diabetes mellitus (TNDM), a rare form of childhood diabetes, to an 5.4 Mb region of chromosome 6q24. We have also shown that TNDM is associated with both paternal uniparental disomy (UPD) of chromosome 6 and paternal duplications of the critical region. The sequencing of P1-derived artificial chromosome clones from within the region of interest has allowed us to further localize the gene and to investigate the methylation status of the region. The gene is now known to reside in a 300–400 kb region of 6q24 which contains several CpG islands. At one island we have demonstrated differential DNA methylation between patients with paternal UPD of chromosome 6 and normal controls. In addition, two patients with TNDM, in whom neither paternal UPD of chromosome 6 nor duplication of 6q24 have been found, show a DNA methylation pattern identical to that of patients with paternal UPD of chromosome 6. Control individuals show a hemizygous methylation pattern. These results show that TNDM can be associated with a methylation change and identify a novel methylation imprint on chromosome 6 associated with TNDM.

Document Type: Research article

Affiliations: 1: The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK, 2: MTL, Children’s Hospital Research Institute, Room 236, 4060 St Catherine Street West, Westmount, Quebec, Canada H3Z 2Z3, 3: Department of Human Genetics, University of Kiel, 24105 Kiel, Germany, 4: Institute of Child Health, St Michael’s Hill, Bristol BS2 8BJ, UK and 5: Wessex Clinical Genetics Service, The Princess Anne Hospital, Southampton SO16 5YA, UK

Publication date: 2000-03-01

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• Human Molecular Genetics concentrates on full-length research papers covering a wide range of topics in all aspects of human molecular genetics.

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• By this author: Gardner, Rebecca J. ;  Mackay, Deborah J.G. ;  Mungall, Andrew J. ;  Polychronakos, Constantin ;  Siebert, Reiner ;  Shield, Julian P.H. ;  Temple, I. Karen ;  Robinson, David O.

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