A Novel KCNJ11 Mutation Associated with Transient Neonatal Diabetes

2.50
Hdl Handle:
http://hdl.handle.net/11287/620889
Title:
A Novel KCNJ11 Mutation Associated with Transient Neonatal Diabetes
Authors:
Gole, E.; Oikonomou, S.; Ellard, Sian ( 0000-0002-7620-5526 ) ; De Franco, E.; Karavanaki, K.
Abstract:
Neonatal diabetes mellitus (NDM) is a rare type of monogenic diabetes that presents in the first 6 months of life. Activating mutations in the KCNJ11 gene encoding for the Kir6.2 subunit of the ATP-sensitive potassium (KATP ) channel can lead to transient NDM (TNDM) or to permanent NDM (PNDM). A female infant presented on the 22nd day of life with severe hyperglycemia and ketoacidosis (glucose: 907mg/dL, blood gas pH: 6.84, HCO3: 6 mmol/L). She was initially managed with intravenous (IV) fluids and IV insulin. Ketoacidosis resolved within 48 hours and she was started on subcutaneous insulin injections with intermediate acting insulin NPH twice daily requiring initially 0.75-1.35 IU/kg/d. Pre-prandial C-peptide levels were 0.51 ng/mL (normal: 1.77-4.68). Insulin requirements were gradually reduced and insulin administration was discontinued at the age of 10 months with subsequent normal glucose and HbA1c levels. C-peptide levels normalized (pre-prandial: 1.6 ng/mL, postprandial: 2 ng/mL). Genetic analysis identified a novel missense mutation (p.Pro254Gln) in the KCNJ11 gene. We report a novel KCNJ11 mutation in a patient who presented in the first month of life with a phenotype of NDM that subsided at the age of 10 months. It is likely that the novel p.P254Q mutation results in mild impairment of the KATP channel function leading to TNDM.
Citation:
A Novel KCNJ11 Mutation Associated with Transient Neonatal Diabetes 2018, 10 (2):175-178 J Clin Res Pediatr Endocrinol
Publisher:
Galenos
Journal:
Journal of clinical research in pediatric endocrinology
Issue Date:
1-Jun-2018
URI:
http://hdl.handle.net/11287/620889
DOI:
10.4274/jcrpe.5166
PubMed ID:
28943514
Additional Links:
https://doi.org/10.4274/jcrpe.5166
Note:
This article is freely available via Open Access.
Type:
Journal Article
Language:
en
ISSN:
1308-5735
Appears in Collections:
Molecular Genetics; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorGole, E.en
dc.contributor.authorOikonomou, S.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorDe Franco, E.en
dc.contributor.authorKaravanaki, K.en
dc.date.accessioned2018-10-11T12:49:50Z-
dc.date.available2018-10-11T12:49:50Z-
dc.date.issued2018-06-01-
dc.identifier.citationA Novel KCNJ11 Mutation Associated with Transient Neonatal Diabetes 2018, 10 (2):175-178 J Clin Res Pediatr Endocrinolen
dc.identifier.issn1308-5735-
dc.identifier.pmid28943514-
dc.identifier.doi10.4274/jcrpe.5166-
dc.identifier.urihttp://hdl.handle.net/11287/620889-
dc.description.abstractNeonatal diabetes mellitus (NDM) is a rare type of monogenic diabetes that presents in the first 6 months of life. Activating mutations in the KCNJ11 gene encoding for the Kir6.2 subunit of the ATP-sensitive potassium (KATP ) channel can lead to transient NDM (TNDM) or to permanent NDM (PNDM). A female infant presented on the 22nd day of life with severe hyperglycemia and ketoacidosis (glucose: 907mg/dL, blood gas pH: 6.84, HCO3: 6 mmol/L). She was initially managed with intravenous (IV) fluids and IV insulin. Ketoacidosis resolved within 48 hours and she was started on subcutaneous insulin injections with intermediate acting insulin NPH twice daily requiring initially 0.75-1.35 IU/kg/d. Pre-prandial C-peptide levels were 0.51 ng/mL (normal: 1.77-4.68). Insulin requirements were gradually reduced and insulin administration was discontinued at the age of 10 months with subsequent normal glucose and HbA1c levels. C-peptide levels normalized (pre-prandial: 1.6 ng/mL, postprandial: 2 ng/mL). Genetic analysis identified a novel missense mutation (p.Pro254Gln) in the KCNJ11 gene. We report a novel KCNJ11 mutation in a patient who presented in the first month of life with a phenotype of NDM that subsided at the age of 10 months. It is likely that the novel p.P254Q mutation results in mild impairment of the KATP channel function leading to TNDM.en
dc.language.isoenen
dc.publisherGalenosen
dc.relation.urlhttps://doi.org/10.4274/jcrpe.5166en
dc.rightsArchived with thanks to Journal of clinical research in pediatric endocrinologyen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subject.meshDiabetes Mellitus-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshInfant, Newborn-
dc.subject.meshInfant, Newborn, Diseases-
dc.subject.meshMutation, Missense-
dc.subject.meshPotassium Channels, Inwardly Rectifying-
dc.titleA Novel KCNJ11 Mutation Associated with Transient Neonatal Diabetesen
dc.typeJournal Articleen
dc.identifier.journalJournal of clinical research in pediatric endocrinologyen
dc.description.noteThis article is freely available via Open Access.en
dc.type.versionPublisheden

Related articles on PubMed

All Items in RD&E Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.