Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family

Bonnefond, A., Vaillant, E., Philippe, J., Skrobek, B., Lobbens, S., Yengo, L., Huyvaert, M., Cave, H., Busiah, K., Scharfmann, R., Polak, M., Abdul-Rasoul, M., Froguel, P. and Vaxillaire, M. (2013) Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family. Diabetes and Metabolism, 39 3: 276-280. doi:10.1016/j.diabet.2013.02.007


Author Bonnefond, A.
Vaillant, E.
Philippe, J.
Skrobek, B.
Lobbens, S.
Yengo, L.
Huyvaert, M.
Cave, H.
Busiah, K.
Scharfmann, R.
Polak, M.
Abdul-Rasoul, M.
Froguel, P.
Vaxillaire, M.
Title Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family
Formatted title
Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family
Journal name Diabetes and Metabolism   Check publisher's open access policy
ISSN 1262-3636
1878-1780
Publication date 2013-05-01
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.diabet.2013.02.007
Open Access Status Not yet assessed
Volume 39
Issue 3
Start page 276
End page 280
Total pages 5
Place of publication Cedex, France
Publisher Elsevier Masson
Language eng
Formatted abstract
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.
Keyword Genetics
Homozygosity mapping
MNX1
NDM
Neonatal diabetes mellitus
ROH
SNP
Transcription factor
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID ERANET-09 RARE-005
ANR-10-LABX-46
2012-SFD-AFD
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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