OBJECTIVES: The factors determining the pathogenesis of transient and permanent neonatal diabetes mellitus are poorly characterized. The purpose of this study was to examine the role of chromosome 6 in the pathogenesis of neonatal diabetes mellitus and to detect differences between these 2 phenotypes. METHODS: Microsatellite markers (D6S334, D6S286, D6S310, D6S308, D6S292, D6S311, and D6S403) and human leukocyte antigen DQ alleles were examined using polymerase chain reaction and DNA fragment electrophoresis in 3 patients with transient and 3 patients with permanent neonatal diabetes mellitus. Humoral markers of islet cell autoimmunity and clinical characteristics were analyzed in the 2 groups. RESULTS: A patient with transient neonatal diabetes mellitus (TND) and macroglossia carrying paternal uniparental isodisomy (UPD) of chromosome 6 has been identified. The isodisomy affected the whole chromosome; no maternal chromosome 6 sequences were detected. The permanent neonatal diabetes mellitus cases and the other 2 cases with TND did not have UPD. None of the patients had high-risk type 1 diabetes human leukocyte antigen DQ alleles and most infants were negative for islet cell-specific autoantibodies indicating that none of the 2 forms of neonatal diabetes mellitus is likely to be of autoimmune origin. An association of TND and persistent granulocytopenia is described for the first time. CONCLUSIONS: We propose that transient and permanent forms of neonatal diabetes mellitus have different genetic background and represent different disease entities. TND is associated with UPD of chromosome 6 suggesting that an imprinted gene on chromosome 6 is responsible for this phenotype. It seems that 2 copies of the paternal allele are necessary for the development of TND; therefore, it is likely that overexpression of a putative gene located on chromosome 6 alters pancreatic beta-cell maturation and insulin secretion.
OBJECTIVES: The factors determining the pathogenesis of transient and permanent neonatal diabetes mellitus are poorly characterized. The purpose of this study was to examine the role of chromosome 6 in the pathogenesis of neonatal diabetes mellitus and to detect differences between these 2 phenotypes. METHODS: Microsatellite markers (D6S334, D6S286, D6S310, D6S308, D6S292, D6S311, and D6S403) and human leukocyte antigen DQ alleles were examined using polymerase chain reaction and DNA fragment electrophoresis in 3 patients with transient and 3 patients with permanent neonatal diabetes mellitus. Humoral markers of islet cell autoimmunity and clinical characteristics were analyzed in the 2 groups. RESULTS: A patient with transient neonatal diabetes mellitus (TND) and macroglossia carrying paternal uniparental isodisomy (UPD) of chromosome 6 has been identified. The isodisomy affected the whole chromosome; no maternal chromosome 6 sequences were detected. The permanent neonatal diabetes mellitus cases and the other 2 cases with TND did not have UPD. None of the patients had high-risk type 1 diabeteshuman leukocyte antigen DQ alleles and most infants were negative for islet cell-specific autoantibodies indicating that none of the 2 forms of neonatal diabetes mellitus is likely to be of autoimmune origin. An association of TND and persistent granulocytopenia is described for the first time. CONCLUSIONS: We propose that transient and permanent forms of neonatal diabetes mellitus have different genetic background and represent different disease entities. TND is associated with UPD of chromosome 6 suggesting that an imprinted gene on chromosome 6 is responsible for this phenotype. It seems that 2 copies of the paternal allele are necessary for the development of TND; therefore, it is likely that overexpression of a putative gene located on chromosome 6 alters pancreatic beta-cell maturation and insulin secretion.
Authors: Céline Huber; Anee-Lise Delezoide; Fabien Guimiot; Clarisse Baumann; Valérie Malan; Martine Le Merrer; Daniela Bezerra Da Silva; Dominique Bonneau; Pierre Chatelain; Carol Chu; Robin Clark; Helen Cox; Patrick Edery; Thomas Edouard; Virginia Fano; Kate Gibson; Gabriele Gillessen-Kaesbach; Maria-Luisa Giovannucci-Uzielli; Luitgard Margarete Graul-Neumann; Johana-Maria van Hagen; Liselot van Hest; Dafne Horovitz; Judith Melki; Carl-Joachim Partsch; Henry Plauchu; Anna Rajab; Massimiliano Rossi; David Sillence; Elisabeth Steichen-Gersdorf; Helen Stewart; Sheila Unger; Martin Zenker; Arnold Munnich; Valérie Cormier-Daire Journal: Eur J Hum Genet Date: 2008-10-29 Impact factor: 4.246
Authors: S Das; C M Lese; M Song; J L Jensen; L A Wells; B L Barnoski; J A Roseberry; J M Camacho; D H Ledbetter; R E Schnur Journal: Am J Hum Genet Date: 2000-10-18 Impact factor: 11.025
Authors: Amanda R Dahl; Radhika Dhamija; Alaa Al Nofal; Siobhan T Pittock; W Frederick Schwenk; Seema Kumar Journal: J Clin Res Pediatr Endocrinol Date: 2017-08-02