Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00508188" target="_blank" >RIV/68378050:_____/19:00508188 - isvavai.cz</a>

Result on the web

<a href="https://ng.neurology.org/content/5/2/e320" target="_blank" >https://ng.neurology.org/content/5/2/e320</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1212/NXG.0000000000000320" target="_blank" >10.1212/NXG.0000000000000320</a>

Result language

angličtina

Original language name

Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ

Original language description

Objective To address the relationship between novel mutations in polynucleotide 5'-kinase 3'-phosphatase (PNKP), DNA strand break repair, and neurologic disease. Methods We have employed whole-exome sequencing, Sanger sequencing, and molecular/cellular biology. Results We describe here a patient with microcephaly with early onset seizures (MCSZ) from the Indian sub-continent harboring 2 novel mutations in PNKP, including a pathogenic mutation in the fork-head associated domain. In addition, we confirm that MCSZ is associated with hyperactivation of the single-strand break sensor protein protein poly (ADP-ribose) polymerase 1 (PARP1) following the induction of abortive topoisomerase I activity, a source of DNA strand breakage associated previously with neurologic disease. Conclusions These data expand the spectrum of PNKP mutations associated with MCSZ and show that PARP1 hyperactivation at unrepaired topoisomerase-induced DNA breaks is a molecular feature of this disease.

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

10601 - Cell biology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

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

Name of the periodical

NEUROLOGY-GENETICS

ISSN

2376-7839

e-ISSN

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Volume of the periodical

5

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

7

Pages from-to

e320

UT code for WoS article

000481665200010

EID of the result in the Scopus database

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