ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.

Détails

ID Serval
serval:BIB_5984DFDC9C14
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.
Périodique
Journal of Medical Genetics
Auteur⸱e⸱s
Bellanné-Chantelot C., Saint-Martin C., Ribeiro M.J., Vaury C., Verkarre V., Arnoux J.B., Valayannopoulos V., Gobrecht S., Sempoux C., Rahier J., Fournet J.C., Jaubert F., Aigrain Y., Nihoul-Fékété C., de Lonlay P.
ISSN
1468-6244 (Electronic)
ISSN-L
0022-2593
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
47
Numéro
11
Pages
752-759
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
BACKGROUND: Congenital hyperinsulinism (CHI) is characterised by an over secretion of insulin by the pancreatic β-cells. This condition is mostly caused by mutations in ABCC8 or KCNJ11 genes encoding the SUR1 and KIR6.2 subunits of the ATP-sensitive potassium (K(ATP)) channel. CHI patients are classified according to their responsiveness to diazoxide and to their histopathological diagnosis (either focal, diffuse or atypical forms). Here, we raise the benefits/limits of the genetic diagnosis in the clinical management of CHI patients.
METHODS: ABCC8/KCNJ11 mutational spectrum was established in 109 diazoxide-unresponsive CHI patients for whom an appropriate clinical management is essential to prevent brain damage. Relationships between genotype and radiopathological diagnosis were analysed.
RESULTS: ABCC8 or KCNJ11 defects were found in 82% of the CHI cases. All patients with a focal form were associated with a single K(ATP) channel molecular event. In contrast, patients with diffuse forms were genetically more heterogeneous: 47% were associated with recessively inherited mutations, 34% carried a single heterozygous mutation and 19% had no mutation. There appeared to be a predominance of paternally inherited mutations in patients diagnosed with a diffuse form and carrying a sole K(ATP) channel mutation.
CONCLUSIONS: The identification of recessively inherited mutations related to severe and diffuse forms of CHI provides an informative genetic diagnosis and allows prenatal diagnosis. In contrast, in patients carrying a single K(ATP) channel mutation, genetic analysis should be confronted with the PET imaging to categorise patients as focal or diffuse forms in order to get the appropriate therapeutic management.
Mots-clé
ATP-Binding Cassette Transporters/genetics, Congenital Hyperinsulinism/diagnosis, Congenital Hyperinsulinism/drug therapy, DNA Mutational Analysis, Diazoxide/therapeutic use, Drug Resistance, Female, Genotype, Humans, Infant, Infant, Newborn, Male, Mutation, Potassium Channels, Inwardly Rectifying/genetics, Receptors, Drug/genetics, Sulfonylurea Receptors, Vasodilator Agents/therapeutic use
Pubmed
Web of science
Création de la notice
29/01/2015 13:42
Dernière modification de la notice
20/08/2019 15:13
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