Aims/hypothesis. Investigate the genetic etiology of permanent diabetes mellitus with onset in the first 12 months of age. Methods. We studied forty-six 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 8 subjects with diabetes diagnosed between 7 to 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, NKX6-1 genes and -in selected probands- CACNA1C, GCK, FOXP3, NEUROG3 and CDK4. The incidence rate for PNDM/MDI was calculated using the database of Italian patients collected from 1995-2009. 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 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/interpretation. Genetic mutations were identified in ~75% of non-consanguineous probands with PNDM/MDI by sequential screening of KCNJ11, INS and ABCC8 genes within the first 6 months of age. This percentage decreases to 12% in those with diabetes diagnosed between 7 to 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.

Russo, L., Iafusco, D., Brescianini, S., Nocerino, V., Bizzarri, C., Toni, S., et al. (2011). Permanent diabetes during the first year of life: multiple gene screening in 54 patients. DIABETOLOGIA, 54(7), 1693-1701 [10.1007/s00125-011-2094-8].

Permanent diabetes during the first year of life: multiple gene screening in 54 patients

COLOMBO, CLAUDIO;BARBETTI, FABRIZIO
2011-01-01

Abstract

Aims/hypothesis. Investigate the genetic etiology of permanent diabetes mellitus with onset in the first 12 months of age. Methods. We studied forty-six 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 8 subjects with diabetes diagnosed between 7 to 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, NKX6-1 genes and -in selected probands- CACNA1C, GCK, FOXP3, NEUROG3 and CDK4. The incidence rate for PNDM/MDI was calculated using the database of Italian patients collected from 1995-2009. 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 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/interpretation. Genetic mutations were identified in ~75% of non-consanguineous probands with PNDM/MDI by sequential screening of KCNJ11, INS and ABCC8 genes within the first 6 months of age. This percentage decreases to 12% in those with diabetes diagnosed between 7 to 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.
2011
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/13 - ENDOCRINOLOGIA
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA
English
Con Impact Factor ISI
humans; diabetes mellitus; infant, newborn; sulfonylurea receptors; protein-serine-threonine kinases; insulin; infant; receptors, drug; potassium channels, inwardly rectifying; ATP-binding cassette transporters; genetic predisposition to disease; mutation; female; male
Russo, L., Iafusco, D., Brescianini, S., Nocerino, V., Bizzarri, C., Toni, S., et al. (2011). Permanent diabetes during the first year of life: multiple gene screening in 54 patients. DIABETOLOGIA, 54(7), 1693-1701 [10.1007/s00125-011-2094-8].
Russo, L; Iafusco, D; Brescianini, S; Nocerino, V; Bizzarri, C; Toni, S; Cerutti, F; Monciotti, C; Pesavento, R; Iughetti, L; Bernardini, L; Bonfanti, R; Gargantini, L; Vanelli, M; Aguilar Bryan, L; Stazi, M; Grasso, V; Colombo, C; Barbetti, F
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
Diab in the 1st year of life.pdf

accesso aperto

Descrizione: articolo principale
Dimensione 194.16 kB
Formato Adobe PDF
194.16 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/55341
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 60
  • ???jsp.display-item.citation.isi??? 48
social impact