Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373481" target="_blank" >RIV/00216208:11130/17:10373481 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00064203:_____/17:10373481
Výsledek na webu
<a href="https://doi.org/10.1515/jpem-2017-0163" target="_blank" >https://doi.org/10.1515/jpem-2017-0163</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1515/jpem-2017-0163" target="_blank" >10.1515/jpem-2017-0163</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?
Popis výsledku v původním jazyce
Background: Congenital hyperinsulinism (CHI) is frequently caused by mutations in one of the K-ATP channel subunits encoded by the genes ABCC8 and KCNJ11. The effect of simultaneous mutations in both of these genes on the pancreatic beta-cell function is not known and patients with CHI carrying both ABCC8 and KCNJ11 mutations have not yet been reported. We questioned if a combination of heterozygous mutations in the ABCC8 and KCNJ11 genes could also lead to beta-cell dysfunction presenting as CHI. Methods: As a model, we used a patient with transient CHI that paternally inherited novel heterozygous mutations in ABCC8 (p.Tyr1293Asp) and KCNJ11 (p.Arg50Trp) genes. The pathogenic effects on the pancreatic beta-cells function were examined in an in vitro functional study using radioactive rubidium efflux assay. Results: We showed that the activation of the mutated K-ATP channels by diazoxide was decreased by 60.9% in the channels with the heterozygous combination of both mutations compared to the wild type channels. This could indicate the pathogenic effect on the pancreatic beta-cell function leading to CHI although conclusive evidence is needed to be added. Conclusions: Our findings may widen the spectrum of genetic causes of CHI and suggest a novel pathogenic mechanism of CHI that must however, be further investigated.
Název v anglickém jazyce
Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?
Popis výsledku anglicky
Background: Congenital hyperinsulinism (CHI) is frequently caused by mutations in one of the K-ATP channel subunits encoded by the genes ABCC8 and KCNJ11. The effect of simultaneous mutations in both of these genes on the pancreatic beta-cell function is not known and patients with CHI carrying both ABCC8 and KCNJ11 mutations have not yet been reported. We questioned if a combination of heterozygous mutations in the ABCC8 and KCNJ11 genes could also lead to beta-cell dysfunction presenting as CHI. Methods: As a model, we used a patient with transient CHI that paternally inherited novel heterozygous mutations in ABCC8 (p.Tyr1293Asp) and KCNJ11 (p.Arg50Trp) genes. The pathogenic effects on the pancreatic beta-cells function were examined in an in vitro functional study using radioactive rubidium efflux assay. Results: We showed that the activation of the mutated K-ATP channels by diazoxide was decreased by 60.9% in the channels with the heterozygous combination of both mutations compared to the wild type channels. This could indicate the pathogenic effect on the pancreatic beta-cell function leading to CHI although conclusive evidence is needed to be added. Conclusions: Our findings may widen the spectrum of genetic causes of CHI and suggest a novel pathogenic mechanism of CHI that must however, be further investigated.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30202 - Endocrinology and metabolism (including diabetes, hormones)
Návaznosti výsledku
Projekt
—
Návaznosti
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2017
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Pediatric Endocrinology & Metabolism
ISSN
0334-018X
e-ISSN
—
Svazek periodika
30
Číslo periodika v rámci svazku
12
Stát vydavatele periodika
DE - Spolková republika Německo
Počet stran výsledku
5
Strana od-do
1311-1315
Kód UT WoS článku
000416610500013
EID výsledku v databázi Scopus
2-s2.0-85037078545