Genetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates.

2.50
Hdl Handle:
http://hdl.handle.net/11287/618143
Title:
Genetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates.
Authors:
Deeb, A.; Habeb, A. M.; Kaplan, W.; Attia, S.; Hadi, S.; Osman, A.; Al-Jubeh, J.; Flanagan, Sarah; DeFranco, Elisa; Ellard, Sian ( 0000-0002-7620-5526 )
Abstract:
Neonatal diabetes mellitus (NDM) can be transient (TNDM) or permanent (PNDM). Data on NDM from the Gulf region are limited to few studies on PNDM.The objective of this study was to describe the genetic and clinical spectrum of NDM and estimate its incidence in AbuDhabi, capital of the United Arab Emirate (UAE). Patients were identified from the pediatric diabetes clinics and sequencing of known NDM genes was conducted in all families. Twenty-five patients were identified. Incidence during 1985-2013 was 1:29,241 Live births. Twenty-three out of twenty-five had PNDM (incidence 1:31,900) and 2/25 had TNDM (incidence 1:350,903). Eleven out of twenty-five had extra-pancreatic features and three had pancreatic aplasia. The genetic cause was detected in 21/25 (84%). Of the PNDM patients, nine had recessive EIF2AK3 mutations, six had homozygous INS mutations, two with deletion of the PTF1A enhancer, one was heterozygous for KCNJ11 mutation, one harboured a novel ABCC8 variant, and 4/21 without mutations in all known PNDM genes. One TNDM patient had a 6q24 methylation defect and another was homozygous for the INS c-331C>G mutation. This mutation also caused permanent diabetes with variable age of onset from birth to 18 years. The parents of a child with Wolcott-Rallison syndrome had a healthy girl following pre-implantation genetic diagnosis. The child with KCNJ11 mutation was successfully switched from insulin to oral sulphonylurea. The incidence of PNDM in Abu Dhabi is among the highest in the world and its spectrum is different from Europe and USA. In our cohort, genetic testing has significant implications for the clinical management.
Citation:
Genetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates. 2016, 170 (3):602-9 Am. J. Med. Genet. A
Publisher:
Wiley
Journal:
American Journal of Medical Genetics. Part A
Issue Date:
Mar-2016
URI:
http://hdl.handle.net/11287/618143
DOI:
10.1002/ajmg.a.37419
PubMed ID:
26463504
Additional Links:
http://dx.doi.org/10.1002/ajmg.a.37419
Type:
Journal Article
Language:
en
ISSN:
1552-4833
Appears in Collections:
Molecular Genetics; Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorDeeb, A.en
dc.contributor.authorHabeb, A. M.en
dc.contributor.authorKaplan, W.en
dc.contributor.authorAttia, S.en
dc.contributor.authorHadi, S.en
dc.contributor.authorOsman, A.en
dc.contributor.authorAl-Jubeh, J.en
dc.contributor.authorFlanagan, Sarahen
dc.contributor.authorDeFranco, Elisaen
dc.contributor.authorEllard, Sianen
dc.date.accessioned2016-08-10T09:20:56Z-
dc.date.available2016-08-10T09:20:56Z-
dc.date.issued2016-03-
dc.identifier.citationGenetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates. 2016, 170 (3):602-9 Am. J. Med. Genet. Aen
dc.identifier.issn1552-4833-
dc.identifier.pmid26463504-
dc.identifier.doi10.1002/ajmg.a.37419-
dc.identifier.urihttp://hdl.handle.net/11287/618143-
dc.description.abstractNeonatal diabetes mellitus (NDM) can be transient (TNDM) or permanent (PNDM). Data on NDM from the Gulf region are limited to few studies on PNDM.The objective of this study was to describe the genetic and clinical spectrum of NDM and estimate its incidence in AbuDhabi, capital of the United Arab Emirate (UAE). Patients were identified from the pediatric diabetes clinics and sequencing of known NDM genes was conducted in all families. Twenty-five patients were identified. Incidence during 1985-2013 was 1:29,241 Live births. Twenty-three out of twenty-five had PNDM (incidence 1:31,900) and 2/25 had TNDM (incidence 1:350,903). Eleven out of twenty-five had extra-pancreatic features and three had pancreatic aplasia. The genetic cause was detected in 21/25 (84%). Of the PNDM patients, nine had recessive EIF2AK3 mutations, six had homozygous INS mutations, two with deletion of the PTF1A enhancer, one was heterozygous for KCNJ11 mutation, one harboured a novel ABCC8 variant, and 4/21 without mutations in all known PNDM genes. One TNDM patient had a 6q24 methylation defect and another was homozygous for the INS c-331C>G mutation. This mutation also caused permanent diabetes with variable age of onset from birth to 18 years. The parents of a child with Wolcott-Rallison syndrome had a healthy girl following pre-implantation genetic diagnosis. The child with KCNJ11 mutation was successfully switched from insulin to oral sulphonylurea. The incidence of PNDM in Abu Dhabi is among the highest in the world and its spectrum is different from Europe and USA. In our cohort, genetic testing has significant implications for the clinical management.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://dx.doi.org/10.1002/ajmg.a.37419en
dc.rightsArchived with thanks to American journal of medical genetics. Part Aen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleGenetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates.en
dc.typeJournal Articleen
dc.identifier.journalAmerican Journal of Medical Genetics. Part Aen
dc.type.versionPublisheden

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