Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6

Robert Hermann, Antti Pekka Laine, Calle Johansson, Tamas Niederland, Lidia Tokarska, Hanna Dziatkowiak, Jorma Ilonen, G. Soltész

Research output: Contribution to journalArticle

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Abstract

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 β-cell maturation and insulin secretion.

Original languageEnglish
Pages (from-to)49-52
Number of pages4
JournalPediatrics
Volume105
Issue number1 I
Publication statusPublished - Jan 2000

Fingerprint

Uniparental Disomy
Chromosomes, Human, Pair 6
Diabetes Mellitus
Alleles
HLA Antigens
Islets of Langerhans
Macroglossia
Phenotype
Agranulocytosis
Permanent Neonatal Diabetes Mellitus
Autoimmunity
Type 1 Diabetes Mellitus
Microsatellite Repeats
Autoantibodies
Genes
Electrophoresis
Chromosomes
Mothers
Insulin
Polymerase Chain Reaction

Keywords

  • Chromosome 6
  • Imprinted gene
  • Transient neonatal diabetes mellitus
  • Uniparental disomy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Hermann, R., Laine, A. P., Johansson, C., Niederland, T., Tokarska, L., Dziatkowiak, H., ... Soltész, G. (2000). Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6. Pediatrics, 105(1 I), 49-52.

Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6. / Hermann, Robert; Laine, Antti Pekka; Johansson, Calle; Niederland, Tamas; Tokarska, Lidia; Dziatkowiak, Hanna; Ilonen, Jorma; Soltész, G.

In: Pediatrics, Vol. 105, No. 1 I, 01.2000, p. 49-52.

Research output: Contribution to journalArticle

Hermann, R, Laine, AP, Johansson, C, Niederland, T, Tokarska, L, Dziatkowiak, H, Ilonen, J & Soltész, G 2000, 'Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6', Pediatrics, vol. 105, no. 1 I, pp. 49-52.
Hermann R, Laine AP, Johansson C, Niederland T, Tokarska L, Dziatkowiak H et al. Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6. Pediatrics. 2000 Jan;105(1 I):49-52.
Hermann, Robert ; Laine, Antti Pekka ; Johansson, Calle ; Niederland, Tamas ; Tokarska, Lidia ; Dziatkowiak, Hanna ; Ilonen, Jorma ; Soltész, G. / Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6. In: Pediatrics. 2000 ; Vol. 105, No. 1 I. pp. 49-52.
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abstract = "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 β-cell maturation and insulin secretion.",
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T1 - Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6

AU - Hermann, Robert

AU - Laine, Antti Pekka

AU - Johansson, Calle

AU - Niederland, Tamas

AU - Tokarska, Lidia

AU - Dziatkowiak, Hanna

AU - Ilonen, Jorma

AU - Soltész, G.

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Y1 - 2000/1

N2 - 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 β-cell maturation and insulin secretion.

AB - 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 β-cell maturation and insulin secretion.

KW - Chromosome 6

KW - Imprinted gene

KW - Transient neonatal diabetes mellitus

KW - Uniparental disomy

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VL - 105

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JO - Pediatrics

JF - Pediatrics

SN - 0031-4005

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