Permanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation in NEUROD1.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620660
Title:
Permanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation in NEUROD1.
Authors:
Demirbilek, H.; Hatipoglu, N.; Gul, U.; Tatli, Z. U.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Flanagan, S. E.; De Franco, E.; Kurtoglu, S.
Abstract:
The basic helix-loop-helix (bHLH) transcription factor, neuronal differentiation 1 (NEUROD1) (also known as BETA2) is involved in the development of neural elements and endocrine pancreas. Less than 10 reports of adult-onset non-insulin-dependent diabetes mellitus (NIDDM) due to heterozygous NEUROD1 mutations and 2 cases with permanent neonatal diabetes mellitus (PNDM) and neurological abnormalities due to homozygous NEUROD1 mutations have been published. A 13 year-old female was referred to endocrine department due to hyperglycemia. She was on insulin therapy following a diagnosis of neonatal diabetes mellitus (NDM) at the age of 9-weeks but missed regular follow-up. Parents are second cousin. There was a significant family history of adult onset NIDDM including patient's father. Auxological measurements were within normal ranges. On laboratory examination blood glucose was 33.2 mmol/L with undetectable c-peptide and glycosylated hemoglobin level of 8.9% (73.8 mmol/mol). She had developed difficulty in walking at the age of 4 years which had worsened over time. On further evaluation, a diagnosis of visual impairment, mental retardation, ataxic gait, retinitis pigmentosa and sensory-neural deafness were considered. Cranial magnetic resonance imaging revealed cerebellar hypoplasia. Molecular genetic analysis using targeted next generation sequencing detected a novel homozygous missense mutation, p.Ile150Asn(c.449T>A), in NEUROD1. Both parents and 2 unaffected siblings were heterozygous for the mutation. We report the third case of PNDM with neurological abnormalities caused by homozygous NEUROD1 mutation, the first caused by a missense mutation. Heterozygous carriers of the p.Ile150Asn mutation were either unaffected or diagnosed with diabetes in adulthood. It is currently unclear whether the NEUROD1 heterozygous mutation has contributed to diabetes development in these individuals.
Citation:
Permanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation in NEUROD1. 2018 Pediatr Diabetes
Publisher:
Wiley
Journal:
Pediatric diabetes
Issue Date:
9-Mar-2018
URI:
http://hdl.handle.net/11287/620660
DOI:
10.1111/pedi.12669
PubMed ID:
29521454
Additional Links:
http://dx.doi.org/10.1111/pedi.12669
Type:
Case Report
Language:
en
ISSN:
1399-5448
Appears in Collections:
Molecular Genetics; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorDemirbilek, H.en
dc.contributor.authorHatipoglu, N.en
dc.contributor.authorGul, U.en
dc.contributor.authorTatli, Z. U.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorFlanagan, S. E.en
dc.contributor.authorDe Franco, E.en
dc.contributor.authorKurtoglu, S.en
dc.date.accessioned2018-03-27T13:16:30Z-
dc.date.available2018-03-27T13:16:30Z-
dc.date.issued2018-03-09-
dc.identifier.citationPermanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation in NEUROD1. 2018 Pediatr Diabetesen
dc.identifier.issn1399-5448-
dc.identifier.pmid29521454-
dc.identifier.doi10.1111/pedi.12669-
dc.identifier.urihttp://hdl.handle.net/11287/620660-
dc.description.abstractThe basic helix-loop-helix (bHLH) transcription factor, neuronal differentiation 1 (NEUROD1) (also known as BETA2) is involved in the development of neural elements and endocrine pancreas. Less than 10 reports of adult-onset non-insulin-dependent diabetes mellitus (NIDDM) due to heterozygous NEUROD1 mutations and 2 cases with permanent neonatal diabetes mellitus (PNDM) and neurological abnormalities due to homozygous NEUROD1 mutations have been published. A 13 year-old female was referred to endocrine department due to hyperglycemia. She was on insulin therapy following a diagnosis of neonatal diabetes mellitus (NDM) at the age of 9-weeks but missed regular follow-up. Parents are second cousin. There was a significant family history of adult onset NIDDM including patient's father. Auxological measurements were within normal ranges. On laboratory examination blood glucose was 33.2 mmol/L with undetectable c-peptide and glycosylated hemoglobin level of 8.9% (73.8 mmol/mol). She had developed difficulty in walking at the age of 4 years which had worsened over time. On further evaluation, a diagnosis of visual impairment, mental retardation, ataxic gait, retinitis pigmentosa and sensory-neural deafness were considered. Cranial magnetic resonance imaging revealed cerebellar hypoplasia. Molecular genetic analysis using targeted next generation sequencing detected a novel homozygous missense mutation, p.Ile150Asn(c.449T>A), in NEUROD1. Both parents and 2 unaffected siblings were heterozygous for the mutation. We report the third case of PNDM with neurological abnormalities caused by homozygous NEUROD1 mutation, the first caused by a missense mutation. Heterozygous carriers of the p.Ile150Asn mutation were either unaffected or diagnosed with diabetes in adulthood. It is currently unclear whether the NEUROD1 heterozygous mutation has contributed to diabetes development in these individuals.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://dx.doi.org/10.1111/pedi.12669en
dc.rightsArchived with thanks to Pediatric diabetesen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titlePermanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation in NEUROD1.en
dc.typeCase Reporten
dc.identifier.journalPediatric diabetesen
dc.type.versionIn press (epub ahead of print)en

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