title: Abnormalities in chromosome 6q24 as a cause of early-onset, non-obese, non-autoimmune diabetes mellitus without history of neonatal diabetes.
abstract: OBJECTIVE
  Abnormalities in the imprinted locus on chromosome 6q24 are the most common causes of transient neonatal diabetes mellitus (6q24-related transient neonatal diabetes). 6q24-Related transient neonatal diabetes is characterized by the patient being small-for-gestational age, diabetes mellitus at birth, spontaneous remission within the first few months and frequent recurrence of diabetes after childhood. However, it is not clear whether individuals with 6q24 abnormalities invariably develop transient neonatal diabetes. This study explored the possibility that 6q24 abnormalities might cause early-onset, non-autoimmune diabetes without transient neonatal diabetes.
  
  
  METHODS
  The 6q24 imprinted locus was screened for abnormalities in 113 Japanese patients with early-onset, non-obese, non-autoimmune diabetes mellitus who tested negative for mutations in the common maturation-onset diabetes of the young (MODY) genes and without a history of transient neonatal diabetes. Positive patients were further analysed by combined loss of heterozygosity / comparative genomic hybridization analysis and by microsatellite analysis. Detailed clinical data were collected through the medical records of the treating hospitals.
  
  
  RESULTS
  Three patients with paternal uniparental isodisomy of chromosome 6q24 were identified. None presented with hyperglycaemia in the neonatal period. Characteristically, these patients were born small-for-gestational age, representing 27.2% of the 11 patients whose birth weight standard deviation score (SDS) for gestational age was below -2.0.
  
  
  CONCLUSIONS
  Abnormalities in the imprinted locus on chromosome 6q24 do not necessarily cause transient neonatal diabetes. Non-penetrant 6q24-related diabetes could be an underestimated cause of early-onset, non-autoimmune diabetes in patients who are not obese and born small-for-gestational age.
authors: Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan.|Department of Genetic Medicine, Osaka City General Hospital, Osaka, Japan.|Clinical Research Center, Osaka City General Hospital, Osaka, Japan.
authors: T
authors: T
authors: Yorifuji
authors: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors: K
authors: K
authors: Matsubara
authors: Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan.
authors: A
authors: A
authors: Sakakibara
authors: Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan.
authors: Y
authors: Y
authors: Hashimoto
authors: Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan.
authors: R
authors: R
authors: Kawakita
authors: Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan.
authors: Y
authors: Y
authors: Hosokawa
authors: Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan.
authors: R
authors: R
authors: Fujimaru
authors: Department of Genetic Medicine, Osaka City General Hospital, Osaka, Japan.
authors: A
authors: A
authors: Murakami
authors: Department of Genetic Medicine, Osaka City General Hospital, Osaka, Japan.
authors: N
authors: N
authors: Tamagawa
authors: Clinical Research Center, Osaka City General Hospital, Osaka, Japan.
authors: K
authors: K
authors: Hatake
authors: Department of Pediatrics, Takarazuka City Hospital, Japan.
authors: H
authors: H
authors: Nagasaka
authors: Department of Pediatrics, Nihon University School of Medicine, Japan.
authors: J
authors: J
authors: Suzuki
authors: Department of Pediatrics, Nihon University School of Medicine, Japan.
authors: T
authors: T
authors: Urakami
authors: Department of Endocrinology and Metabolism, Aichi Children's Health and Medical Center, Japan.
authors: M
authors: M
authors: Izawa
authors: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors: M
authors: M
authors: Kagami
mesh_terms: D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D015992:Body Mass Index; D002648:Child; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D002896:Chromosomes, Human, Pair 6; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis; D003937:Diagnosis, Differential; D005192:Family Health; D005260:Female; D056426:Genetic Loci; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D007564:Japan; D008297:Male; D055815:Young Adult; D000096803:Imprinting Disorders