A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620318
Title:
A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia.
Authors:
Flanagan, S E; Vairo, F; Johnson, M B; Caswell, R; Laver, T W; Lango Allen, H; Hussain, K; Ellard, Sian ( 0000-0002-7620-5526 )
Abstract:
Congenital hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or it may present as part of a wider syndrome. For approximately 40%-50% of individuals with this condition, sequence analysis of the known HH genes identifies a causative mutation. Identifying the underlying genetic aetiology in the remaining cases is important as a genetic diagnosis will inform on recurrence risk, may guide medical management and will provide valuable insights into β-cell physiology. We sequenced the exome of a child with persistent diazoxide-responsive HH, mild aortic insufficiency, severe hypotonia, and developmental delay as well as the unaffected parents. This analysis identified a de novo mutation, p.G403D, in the proband's CACNA1D gene. CACNA1D encodes the main L-type voltage-gated calcium channel in the pancreatic β-cell, a key component of the insulin secretion pathway. The p.G403D mutation had been reported previously as an activating mutation in an individual with primary hyper-aldosteronism, neuromuscular abnormalities, and transient hypoglycaemia. Sequence analysis of the CACNA1D gene in 60 further cases with HH did not identify a pathogenic mutation. Identification of an activating CACNA1D mutation in a second patient with congenital HH confirms the aetiological role of CACNA1D mutations in this disorder. A genetic diagnosis is important as treatment with a calcium channel blocker may be an option for the medical management of this patient.
Citation:
A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. 2017 Pediatr Diabetes
Publisher:
Wiley
Journal:
Pediatric Diabetes
Issue Date:
20-Mar-2017
URI:
http://hdl.handle.net/11287/620318
DOI:
10.1111/pedi.12512
PubMed ID:
28318089
Additional Links:
http://dx.doi.org/10.1111/pedi.12512
Type:
Case Report
Language:
en
ISSN:
1399-5448
Appears in Collections:
Molecular Genetics; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorFlanagan, S Een
dc.contributor.authorVairo, Fen
dc.contributor.authorJohnson, M Ben
dc.contributor.authorCaswell, Ren
dc.contributor.authorLaver, T Wen
dc.contributor.authorLango Allen, Hen
dc.contributor.authorHussain, Ken
dc.contributor.authorEllard, Sianen
dc.date.accessioned2017-03-24T16:18:40Z-
dc.date.available2017-03-24T16:18:40Z-
dc.date.issued2017-03-20-
dc.identifier.citationA CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. 2017 Pediatr Diabetesen
dc.identifier.issn1399-5448-
dc.identifier.pmid28318089-
dc.identifier.doi10.1111/pedi.12512-
dc.identifier.urihttp://hdl.handle.net/11287/620318-
dc.description.abstractCongenital hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or it may present as part of a wider syndrome. For approximately 40%-50% of individuals with this condition, sequence analysis of the known HH genes identifies a causative mutation. Identifying the underlying genetic aetiology in the remaining cases is important as a genetic diagnosis will inform on recurrence risk, may guide medical management and will provide valuable insights into β-cell physiology. We sequenced the exome of a child with persistent diazoxide-responsive HH, mild aortic insufficiency, severe hypotonia, and developmental delay as well as the unaffected parents. This analysis identified a de novo mutation, p.G403D, in the proband's CACNA1D gene. CACNA1D encodes the main L-type voltage-gated calcium channel in the pancreatic β-cell, a key component of the insulin secretion pathway. The p.G403D mutation had been reported previously as an activating mutation in an individual with primary hyper-aldosteronism, neuromuscular abnormalities, and transient hypoglycaemia. Sequence analysis of the CACNA1D gene in 60 further cases with HH did not identify a pathogenic mutation. Identification of an activating CACNA1D mutation in a second patient with congenital HH confirms the aetiological role of CACNA1D mutations in this disorder. A genetic diagnosis is important as treatment with a calcium channel blocker may be an option for the medical management of this patient.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://dx.doi.org/10.1111/pedi.12512en
dc.rightsArchived with thanks to Pediatric diabetesen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleA CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia.en
dc.typeCase Reporten
dc.identifier.journalPediatric Diabetesen
dc.type.versionIn press (epub ahead of print)en

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