Relevance to Autism

SCID mice, which are homozygous for the severe combined immune deficiency (SCID) spontaneous mutation Prkdcscid, were shown to exhibit social deficits and hyper-connectivity between mutiple brain regions that could be rescued by repopulation of the adaptive immune system (Filiano et al., 2016). Three novel de novo predicted damaging missense variants in PRKDC were observed in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). A SCID patient with compound heterozygous variants in PRKDC was also found to exhibit dysmorphic features, severe growth failure, microcephaly, seizures, and developmental delay (Woodbine et al., 2013). Two non-synonymous postzygotic mosaic mutations (PZMs) in the PRKDC gene were identified in ASD probands (one previously identified variant from Iossifov et al., 2014, and a novel variant in Lim et al., 2017); comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected genome-wide based on background rates (2/571 observed vs. 30/84,448 expected; hypergeometric P-value 0.018).

Molecular Function

This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) and functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. Homozygous or compound heterozygous mutations in the PRKDC gene are responsible for immunodeficiency 26, with or without neurologic abnormalities (IMD26; OMIM 615966)

External Links

References