Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?

Result code in 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>

Alternative codes found

RIV/00064203:_____/17:10373481

Result on the web

<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>

Result language

angličtina

Original language name

Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Pediatric Endocrinology &amp; Metabolism

ISSN

0334-018X

e-ISSN

—

Volume of the periodical

30

Issue of the periodical within the volume

12

Country of publishing house

DE - GERMANY

Number of pages

5

Pages from-to

1311-1315

UT code for WoS article

000416610500013

EID of the result in the Scopus database

2-s2.0-85037078545