cc D81.0

Very rare immune deficiency syndrome characterized by a mutation in the PRKDC gene that presents as a classic SCID syndrome. Patients with this mutation do not differ from patients with a recombination activating gene or Artemis deficiency (van der Burg M et al. 2009).

In a Turkish girl with IMD26, van der Burg et al. (2009) identified a homozygous missense mutation in the PRKDC gene (L3062R; 600899.0001).

Woodbine et al. (2013) found a heterozygous mixed mutation in the PRKDC gene (A3574V, 600899.0002 and EX16del, 600899.0003) in a boy with IMD26 and profound neurological abnormalities. Functional studies revealed loss of function leading to decreased protein expression, loss of kinase activity, and impaired non-homologous end joining (NHEJ) and DSB repair.

Woodbine et al (2013) found a heterozygous mixed mutations in the PRKDC gene (A3574V, 600899.0002 and EX16del, 600899.0003) in a boy with IMD26 and profound neurological abnormalities. The patient suffered from SCID with reduced or absent T and B cells. Furthermore, the was dysmorphic, had severe growth retardation, microcephaly, and seizures, and had profound, globally impaired neurologic function. MRI scans showed cortical and hippocampal dysplasia associated with microcephaly and progressive atrophy over two years of life. DNA-PKcs was shown to be mandatory during human neuronal development. It is likely that high DNA-PK protein expression is required for efficient pre- and postnatal neurogenesis (Woodbine et al. 2013).

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3. van der Burg M et al (2009) DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining. J Clin Invest 119: 91-98.
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