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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family
Diabetes and Metabolism, Volume 39, No. 3, Year 2013
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Description
Aim: Permanent neonatal diabetes mellitus (PNDM) is a rare monogenic form of non-autoimmune diabetes. Genetic defects have been identified in. ∼ 60% of cases, with mutations in ABCC8, KCNJ11 and INS being the most frequent causes of PNDM. Recognition of genetic subtypes strongly impacts on both patients' care and family counseling. This study aimed to identify the genetic aetiology of PNDM in a diabetic girl born of consanguineous parents. Methods: DNA samples from both the proband and her non-diabetic parents were analyzed for homozygosity mapping, using Illumina Infinium 660. K SNP microarrays, focusing on the runs of homozygosity (ROHs) detected only in the patient. Standard Sanger sequencing of candidate genes (MNX1 and GATA6) present in the ROHs was subsequently performed, as well as expression analyses on human embryonic and adult pancreatic islet samples. Results: A putative causal homozygous mutation in the transcription factor gene MNX1 (c.816C>A/p.Phe272Leu) was identified in the PNDM patient, who was clinically diagnosed as a typical case of PNDM with no developmental pancreatic defects or other clinical features. The probable deleterious mutation was located within the MNX1 homeodomain helix 2 that is highly conserved between species. In human embryonic pancreatic islet samples, it has been shown that MNX1 expression is significantly enriched in pancreatic epithelium compared with mesenchyme, suggesting a role for MNX1 in human pancreatic beta-cell development. Conclusion: This study found a new putative cause of PNDM in a consanguineous family. Replication in other cohorts would help to clarify the clinical spectrum of MNX1 mutations in PNDM patients. © 2013 Elsevier Masson SAS.
Authors & Co-Authors
Bonnefond, Amélie
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
Vaillant, Emmanuel
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
Philippe, J.
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
Skrobek, Boris
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
Lobbens, Stéphane
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
Yengo, Loic
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
Huyvaert, Marlène
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
Cavé, Hélène
France, Paris
Hôpital Robert-debré Ap-hp
Busiah, Kanetee
France, Paris
Inserm
France, Paris
Hôpital Necker Enfants Malades
Scharfmann, Raphaël
France, Paris
Inserm
Polak, Michel
France, Paris
Inserm
France, Paris
Hôpital Necker Enfants Malades
Abdul-Rasoul, Majedah M.
Kuwait, Kuwait City
Kuwait University
Froguel, Philippe
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
United Kingdom, London
Hammersmith Hospital
Vaxillaire, Martine
France, Lille
European Institute Genomic for Diabetes Egid
France, Lille
Institut Pasteur de Lille
France, Lille
Université de Lille
Statistics
Citations: 14
Authors: 14
Affiliations: 8
Identifiers
Doi:
10.1016/j.diabet.2013.02.007
ISSN:
12623636
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Noncommunicable Diseases
Study Design
Cohort Study
Participants Gender
Female