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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in human insulin secretion
Diabetologia, Volume 55, No. 9, Year 2012
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Description
Aims: The gene SLC2A2 encodes GLUT2, which is found predominantly in pancreas, liver, kidney and intestine. In mice, GLUT2 is the major glucose transporter into pancreatic beta cells, and biallelic Slc2a2 inactivation causes lethal neonatal diabetes. The role of GLUT2 in human beta cells is controversial, and biallelic SLC2A2 mutations cause Fanconi-Bickel syndrome (FBS), with diabetes rarely reported. We investigated the potential role of GLUT2 in the neonatal period by testing whether SLC2A2 mutations can present with neonatal diabetes before the clinical features of FBS appear. Methods: We studied SLC2A2 in patients with transient neonatal diabetes mellitus (TNDM; n = 25) or permanent neonatal diabetes mellitus (PNDM; n = 79) in whom we had excluded the common genetic causes of neonatal diabetes, using a combined approach of sequencing and homozygosity mapping. Results: Of 104 patients, five (5%) were found to have homozygous SLC2A2 mutations, including four novel mutations (S203R, M376R, c.963+1G>A, F114LfsX16). Four out of five patients with SLC2A2 mutations presented with isolated diabetes and later developed features of FBS. Four out of five patients had TNDM (16% of our TNDM cohort of unknown aetiology). One patient with PNDM remains on insulin at 28 months. Conclusions: SLC2A2 mutations are an autosomal recessive cause of neonatal diabetes that should be considered in consanguineous families or those with TNDM, after excluding common causes, even in the absence of features of FBS. The finding that patients with homozygous SLC2A2 mutations can have neonatal diabetes supports a role for GLUT2 in the human beta cell. © 2012 Springer-Verlag.
Authors & Co-Authors
Sansbury, F. H.
United Kingdom, Exeter
University of Exeter
United Kingdom, Exeter
Royal Devon and Exeter Nhs Foundation Trust
Flanagan, Sarah E.
United Kingdom, Exeter
University of Exeter
Houghton, Jayne A.L.
United Kingdom, Exeter
University of Exeter
United Kingdom, Exeter
Royal Devon and Exeter Nhs Foundation Trust
Shuixian Shen, F. L.
China, Shanghai
Fudan University
Al Senani, Aisha
Oman, Muscat
Royal Hospital
Habeb, Abdelhadi M.
Saudi Arabia, Buraidah
Maternity and Children Hospital
Abdullah, Mohamed Ahmed
Sudan, Khartoum
University of Khartoum Faculty of Medicine
Kariminejad, Ariana
Iran, Tehran
Kariminejad-najmabadi Pathology and Genetics Center
Ellard, Sian
United Kingdom, Exeter
University of Exeter
United Kingdom, Exeter
Royal Devon and Exeter Nhs Foundation Trust
Hattersley, Andrew T.
United Kingdom, Exeter
University of Exeter
United Kingdom, Exeter
Royal Devon and Exeter Nhs Foundation Trust
Statistics
Citations: 117
Authors: 10
Affiliations: 7
Identifiers
Doi:
10.1007/s00125-012-2595-0
ISSN:
0012186X
e-ISSN:
14320428
Research Areas
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Noncommunicable Diseases
Study Design
Cohort Study