title: Permanent diabetes during the first year of life: multiple gene screening in 54 patients.
abstract: OBJECTIVE
  The aim of this study was to investigate the genetic aetiology of permanent diabetes mellitus with onset in the first 12 months of age.
  
  
  METHODS
  We studied 46 probands with permanent, insulin-requiring diabetes with onset within the first 6 months of life (permanent neonatal diabetes mellitus [PNDM]/monogenic diabetes of infancy [MDI]) (group 1) and eight participants with diabetes diagnosed between 7 and 12 months of age (group 2). KCNJ11, INS and ABCC8 genes were sequentially sequenced in all patients. For those who were negative in the initial screening, we examined ERN1, CHGA, CHGB and NKX6-1 genes and, in selected probands, CACNA1C, GCK, FOXP3, NEUROG3 and CDK4. The incidence rate for PNDM/MDI was calculated using a database of Italian patients collected from 1995 to 2009.
  
  
  RESULTS
  In group 1 we found mutations in KCNJ11, INS and ABCC8 genes in 23 (50%), 9 (19.5%) and 4 (8.6%) patients respectively, and a single homozygous mutation in GCK (2.1%). In group 2, we identified one incidence of a KCNJ11 mutation. No genetic defects were detected in other loci. The incidence rate of PNDM/MDI in Italy is estimated to be 1:210,287.
  
  
  CONCLUSIONS
  Genetic mutations were identified in ~75% of non-consanguineous probands with PNDM/MDI, using sequential screening of KCNJ11, INS and ABCC8 genes in infants diagnosed within the first 6 months of age. This percentage decreased to 12% in those with diabetes diagnosed between 7 and 12 months. Patients belonging to the latter group may either carry mutations in genes different from those commonly found in PNDM/MDI or have developed an early-onset form of autoimmune diabetes.
authors.affiliation: Laboratory of Mendelian Diabetes, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Russo
authors.forename: D
authors.initials: D
authors.lastname: Iafusco
authors.forename: S
authors.initials: S
authors.lastname: Brescianini
authors.forename: V
authors.initials: V
authors.lastname: Nocerino
authors.forename: C
authors.initials: C
authors.lastname: Bizzarri
authors.forename: S
authors.initials: S
authors.lastname: Toni
authors.forename: F
authors.initials: F
authors.lastname: Cerutti
authors.forename: C
authors.initials: C
authors.lastname: Monciotti
authors.forename: R
authors.initials: R
authors.lastname: Pesavento
authors.forename: L
authors.initials: L
authors.lastname: Iughetti
authors.forename: L
authors.initials: L
authors.lastname: Bernardini
authors.forename: R
authors.initials: R
authors.lastname: Bonfanti
authors.forename: L
authors.initials: L
authors.lastname: Gargantini
authors.forename: M
authors.initials: M
authors.lastname: Vanelli
authors.forename: L
authors.initials: L
authors.lastname: Aguilar-Bryan
authors.forename: M A
authors.initials: MA
authors.lastname: Stazi
authors.forename: V
authors.initials: V
authors.lastname: Grasso
authors.forename: C
authors.initials: C
authors.lastname: Colombo
authors.forename: F
authors.initials: F
authors.lastname: Barbetti
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D000081410:Germinal Center Kinases; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000235:genetics; D008297:Male; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D000081410:Germinal Center Kinases; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel