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).
ccD81.0
DefinitionThis section has been translated automatically.
EtiopathogenesisThis section has been translated automatically.
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.
Case report(s)This section has been translated automatically.
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).
LiteratureThis section has been translated automatically.
- Araki R et al (1997) Nonsense mutation at tyr-4046 in the DNA-dependent protein kinase catalytic subunit of severe combined immune deficiency mice. Proc Nat Acad Sci 94: 2438-2443.
- Kirchgessner C U et al (1995) DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect. Science 267: 1178-1183.
- 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.
- van der Burg M et al. (2009) DNA-PKcs deficiency in human: long predicted, finally found. Curr Opin Allergy Clin Immunol 9:503-509.
- Wiler R et al (1995) Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA-dependent protein kinase activity. Proc Nat Acad Sci 92: 11485-11489.
- Woodbine L et al (2013) PRKDC mutations in a SCID patient with profound neurological abnormalities. J Clin Invest 123: 2969-2980.