Titre
ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.
Type
article
Institution
Externe
Périodique
Auteur(s)
Bellanné-Chantelot, C.
Auteure/Auteur
Saint-Martin, C.
Auteure/Auteur
Ribeiro, M.J.
Auteure/Auteur
Vaury, C.
Auteure/Auteur
Verkarre, V.
Auteure/Auteur
Arnoux, J.B.
Auteure/Auteur
Valayannopoulos, V.
Auteure/Auteur
Gobrecht, S.
Auteure/Auteur
Sempoux, C.
Auteure/Auteur
Rahier, J.
Auteure/Auteur
Fournet, J.C.
Auteure/Auteur
Jaubert, F.
Auteure/Auteur
Aigrain, Y.
Auteure/Auteur
Nihoul-Fékété, C.
Auteure/Auteur
de Lonlay, P.
Auteure/Auteur
Liens vers les personnes
ISSN
1468-6244
Statut éditorial
Publié
Date de publication
2010
Volume
47
Numéro
11
Première page
752
Dernière page/numéro d’article
759
Peer-reviewed
Oui
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.
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.
PID Serval
serval:BIB_5984DFDC9C14
PMID
Date de création
2015-01-29T11:42:26.488Z
Date de création dans IRIS
2025-05-20T13:41:00Z