The majority of cases of neonatal diabetes in Spain can be explained by known genetic abnormalities
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2007 |
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| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
Diabetic medicine : a journal of the British Diabetic Association - 24(2007), 7 vom: 01. Juli, Seite 707-13 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rica, I [VerfasserIn] |
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| Themen: |
Genetic Markers |
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| Anmerkungen: |
Date Completed 07.11.2007 Date Revised 28.06.2007 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM17017669X |
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| 041 | |a eng | ||
| 100 | 1 | |a Rica, I |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The majority of cases of neonatal diabetes in Spain can be explained by known genetic abnormalities |
| 264 | 1 | |c 2007 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 07.11.2007 | ||
| 500 | |a Date Revised 28.06.2007 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Genetic Markers |2 NLM | |
| 650 | 7 | |a Kir6.2 channel |2 NLM | |
| 650 | 7 | |a Potassium Channels, Inwardly Rectifying |2 NLM | |
| 700 | 1 | |a Luzuriaga, C |e verfasserin |4 aut | |
| 700 | 1 | |a Pérez de Nanclares, G |e verfasserin |4 aut | |
| 700 | 1 | |a Estalella, I |e verfasserin |4 aut | |
| 700 | 1 | |a Aragonés, A |e verfasserin |4 aut | |
| 700 | 1 | |a Barrio, R |e verfasserin |4 aut | |
| 700 | 1 | |a Bilbao, J R |e verfasserin |4 aut | |
| 700 | 1 | |a Carlés, C |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández, C |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández, J M |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández-Rebollo, E |e verfasserin |4 aut | |
| 700 | 1 | |a Gastaldo, E |e verfasserin |4 aut | |
| 700 | 1 | |a Giralt, P |e verfasserin |4 aut | |
| 700 | 1 | |a Gomez Vida, J M |e verfasserin |4 aut | |
| 700 | 1 | |a Gutiérrez, A |e verfasserin |4 aut | |
| 700 | 1 | |a López Siguero, J P |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-Aedo, M J |e verfasserin |4 aut | |
| 700 | 1 | |a Muñoz, M |e verfasserin |4 aut | |
| 700 | 1 | |a Prieto, J |e verfasserin |4 aut | |
| 700 | 1 | |a Rodrigo, J |e verfasserin |4 aut | |
| 700 | 1 | |a Vargas, F |e verfasserin |4 aut | |
| 700 | 1 | |a Castano, L |e verfasserin |4 aut | |
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