title: The majority of cases of neonatal diabetes in Spain can be explained by known genetic abnormalities.
abstract: BACKGROUND
  Neonatal diabetes is a rare disease characterized by hyperglycaemia within the first 3 months of life and requiring insulin treatment; it can either be transient (TNDM) or permanent (PNDM). Alterations at band 6q24 and heterozygous activating mutations in KCNJ11, the gene encoding the pore-forming subunit of the KATP channel, can cause neonatal diabetes. Aims We screened the 6q24 region, KCNJ11, GCK, FOXP3 and IPF1 genes for mutations in families with PNDM or TNDM to establish a phenotype-genotype correlation.
  
  
  METHODS
  Twenty-two patients with neonatal diabetes were recruited. Inclusion criteria were insulin-treated diabetes diagnosed within the first 3 months and insulin treatment for at least 15 days. Clinical data were recorded in a questionnaire.
  
  
  RESULTS
  We identified 17 genetic alterations in our patients: six alterations at the 6q24 band associated with TNDM and nine mutations in KCNJ11, five of which were novel. The analysis for a phenotype-genotype correlation showed that patients with 6q24 alterations had a lower birth weight and were diagnosed earlier than patients with KCNJ11 mutations. At follow-up of the TNDM patients with genetic alterations, 43% developed diabetes or impaired glucose tolerance in later life (one with 6q24 duplication and two with N48D and E227K mutations at KCNJ11 gene). Furthermore, half the first-degree relatives who carried a genetic alteration but who had not suffered from neonatal diabetes were diagnosed with diabetes or impaired glucose tolerance before the age of 30 years.
  
  
  CONCLUSIONS
  KCNJ11 mutations are common in both TNDM and PNDM and are associated with a higher birth weight compared with patients with 6q24 abnormalities. Patients with TNDM should be screened for abnormalities in glucose metabolism in adult life.
authors.affiliation: Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, Basque Country, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Rica
authors.forename: C
authors.initials: C
authors.lastname: Luzuriaga
authors.forename: G
authors.initials: G
authors.lastname: Pérez de Nanclares
authors.forename: I
authors.initials: I
authors.lastname: Estalella
authors.forename: A
authors.initials: A
authors.lastname: Aragonés
authors.forename: R
authors.initials: R
authors.lastname: Barrio
authors.forename: J R
authors.initials: JR
authors.lastname: Bilbao
authors.forename: C
authors.initials: C
authors.lastname: Carlés
authors.forename: C
authors.initials: C
authors.lastname: Fernández
authors.forename: J M
authors.initials: JM
authors.lastname: Fernández
authors.forename: E
authors.initials: E
authors.lastname: Fernández-Rebollo
authors.forename: E
authors.initials: E
authors.lastname: Gastaldo
authors.forename: P
authors.initials: P
authors.lastname: Giralt
authors.forename: J M
authors.initials: JM
authors.lastname: Gomez Vida
authors.forename: A
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: J P
authors.initials: JP
authors.lastname: López Siguero
authors.forename: M J
authors.initials: MJ
authors.lastname: Martínez-Aedo
authors.forename: M
authors.initials: M
authors.lastname: Muñoz
authors.forename: J
authors.initials: J
authors.lastname: Prieto
authors.forename: J
authors.initials: J
authors.lastname: Rodrigo
authors.forename: F
authors.initials: F
authors.lastname: Vargas
authors.forename: L
authors.initials: L
authors.lastname: Castano
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012307:Risk Factors; D013030:Spain; D000099161:Kcnj11 Channel
chemical_list: D005819:Genetic Markers; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel