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Danhauser, K. ; Alhaddad, B. ; Makowski, C.* ; Piekutowska-Abramczuk, D.* ; Syrbe, S.* ; Gomez-Ospina, N.* ; Manning, M.A.* ; Kostera-Pruszczyk, A.* ; Krahn-Peper, C.* ; Berutti, R. ; Kovács-Nagy, R.* ; Gusic, M. ; Graf, E. ; Laugwitz, L.* ; Röblitz, M.* ; Wroblewski, A.* ; Hartmann, H.* ; Das, A.M.* ; Bültmann, E.* ; Fang, F.* ; Xu, M.* ; Schatz, U.A.* ; Karall, D.* ; Zellner, H.* ; Haberlandt, E.* ; Feichtinger, R.G.* ; Mayr, J.A.* ; Meitinger, T. ; Prokisch, H. ; Strom, T.M. ; Płoski, R.* ; Hoffmann, G.F.* ; Pronicki, M.* ; Bonnen, P.E.* ; Morlot, S.* ; Haack, T.B.*

Bi-allelic ADPRHL2 mutations cause neurodegeneration with developmental delay, ataxia, and axaonal neuropathy.

Am. J. Hum. Genet. 103, 817-825 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
ADP-ribosylation is a reversible posttranslational modification used to regulate protein function. ADP-ribosyltransferases transfer ADPribose from NAD(+) to the target protein, and ADP-ribosylhydrolases, such as ADPRHL2, reverse the reaction. We used exome sequencing to identify five different bi-allelic pathogenic ADPRHL2 variants in 12 individuals from 8 families affected by a neurodegenerative disorder manifesting in childhood or adolescence with key clinical features including developmental delay or regression, seizures, ataxia, and axonal (sensori-) motor neuropathy. ADPRHL2 was virtually absent in available affected individuals' fibroblasts, and cell viability was reduced upon hydrogen peroxide exposure, although it was rescued by expression of wild-type ADPRHL2 mRNA as well as treatment with a PARP1 inhibitor. Our findings suggest impaired protein ribosylation as another pathway that, if disturbed, causes neurodegenerative diseases.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Adprhl2 ; Arh3 ; Parp ; Ataxia ; Cerebellar Atrophy ; Neurodegeneration ; Neuropathy ; Posttranslational Modification ; Ribosylation ; Seizure; Poly Adp-ribose; Poly(adp-ribose) Glycohydrolase; Cell-death; Disease; Degradation; Deficiency; Enzymes
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Zeitschrift American Journal of Human Genetics, The
Quellenangaben Band: 103, Heft: 5, Seiten: 817-825 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Institute of Neurogenomics (ING)