PARP10 deficiency manifests by severe developmental delay and DNA repair defect

Maher Awni Shahrour, Claudia M. Nicolae, Simon Edvardson, Motee Ashhab, Adri M. Galvan, Daniel Constantin, Bassam Abu-Libdeh, George Lucian Moldovan, Orly Elpeleg

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


DNA repair mechanisms such as nucleotide excision repair (NER) and translesion synthesis (TLS) are dependent on proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory protein. Recently, homozygosity for p.Ser228Ile mutation in the PCNA gene was reported in patients with neurodegeneration and impaired NER. Using exome sequencing, we identified a homozygous deleterious mutation, c.648delAG, in the PARP10 gene, in a patient suffering from severe developmental delay. In agreement, PARP10 protein was absent from the patient cells. We have previously shown that PARP10 is recruited by PCNA to DNA damage sites and is required for DNA damage resistance. The patient cells were significantly more sensitive to hydroxyurea and UV-induced DNA damage than control cells, resulting in increased apoptosis, indicating DNA repair impairment in the patient cells. PARP10 deficiency joins the long list of DNA repair defects associated with neurodegenerative disorders, including ataxia telangiectasia, xeroderma pigmentosum, Cockayne syndrome, and the recently reported PCNA mutation.

Original languageEnglish (US)
Pages (from-to)227-232
Number of pages6
Issue number4
StatePublished - Oct 1 2016

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience


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