Ghosh, Shereen G., Becker, Kerstin, Huang, He, Salazar, Tracy D., Chai, Guoliang, Salpietro, Vincenzo, Al-Gazali, Lihadh, Waisfisz, Quinten, Wang, Haicui, Vaux, Keith K., Stanley, Valentina, Manole, Andreea, Akpulat, Ugur, Weiss, Marjan M., Efthymiou, Stephanie, Hanna, Michael G., Minetti, Carlo, Striano, Pasquale ORCID: 0000-0002-6065-1476, Pisciotta, Livia, De Grandis, Elisa, Altmueller, Janine, Nuernberg, Peter, Thiele, Holger, Yis, Uluc, Okur, Tuncay Derya, Polat, Ayse Ipek, Amiri, Nafise, Doosti, Mohammad, Karimani, Ehsan Ghayoor, Toosi, Mehran B., Haddad, Gabriel, Karakaya, Mert, Wirth, Brunhilde ORCID: 0000-0003-4051-5191, van Hagen, Johanna M., Wolf, Nicole I., Maroofian, Reza, Houlden, Henry, Cirak, Sebahattin and Gleeson, Joseph G. (2018). Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome. Am. J. Hum. Genet., 103 (3). S. 431 - 440. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

Full text not available from this repository.

Abstract

ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ghosh, Shereen G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, HeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salazar, Tracy D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chai, GuoliangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salpietro, VincenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al-Gazali, LihadhUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waisfisz, QuintenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, HaicuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vaux, Keith K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stanley, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manole, AndreeaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Akpulat, UgurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiss, Marjan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Efthymiou, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hanna, Michael G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Minetti, CarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Striano, PasqualeUNSPECIFIEDorcid.org/0000-0002-6065-1476UNSPECIFIED
Pisciotta, LiviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Grandis, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yis, UlucUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Okur, Tuncay DeryaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Polat, Ayse IpekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amiri, NafiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doosti, MohammadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karimani, Ehsan GhayoorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toosi, Mehran B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haddad, GabrielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karakaya, MertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirth, BrunhildeUNSPECIFIEDorcid.org/0000-0003-4051-5191UNSPECIFIED
van Hagen, Johanna M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, Nicole I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maroofian, RezaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Houlden, HenryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cirak, SebahattinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gleeson, Joseph G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-173157
DOI: 10.1016/j.ajhg.2018.07.010
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 103
Number: 3
Page Range: S. 431 - 440
Date: 2018
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POLY(ADP-RIBOSE) GLYCOHYDROLASE; POLYMERASE-1; RIBOSYLATION; DROSOPHILA; ARH3; PARMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17315

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item