Limited role of interferon-kappa (IFNK) truncating mutations in common variable immunodeficiency.
We used whole exome sequencing to determine the genetic background of CVID in two non-consanguineous German families. We identified IFNK (interferon-kappa) as the only candidate gene that harbored truncating mutations in affected members from both families. One family segregated c.30_31insTGTT, a known frameshift variant, while the other family segregated the novel IFNK mutation p.K199X that creates a premature stop codon. We sequenced the whole coding region of IFNK in a further series of 167 CVID patients and 192 healthy controls. Frameshift mutation c.30_31insTGTT was identified in 12 cases and 17 controls (OR 0.79, 95% CI 0.33-1.81, p=0.79), whereas the p.K199X mutation remained restricted to the original family. No additional truncating variants were found. We conclude that, given their frequent occurrence in non-diseased family members and controls, it is unlikely that truncating variants in IFNK constitute a major factor in the development of CVID.
Department for Clinical Immunology and Rheumatology, Hannover Medical School, Germany. Electronic address: Atschekzei.Faranaz@mh-hannover.de.
Faranaz
F
Atschekzei
Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Thilo
T
Dörk
Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Peter
P
Schürmann
Helmholtz Centre for Infection Research, Braunschweig, Germany.
Robert
R
Geffers
Department for Clinical Immunology and Rheumatology, Hannover Medical School, Germany.
Torsten
T
Witte
Department for Clinical Immunology and Rheumatology, Hannover Medical School, Germany.
Reinhold E
RE
Schmidt
D000328:Adult; D000368:Aged; D017074:Common Variable Immunodeficiency / Q000151:congenital / Q000235:genetics* / Q000276:immunology*; D005260:Female; D016368:Frameshift Mutation; D015894:Genome, Human; D005858:Germany; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA; D000073359:Exome Sequencing
D007370:Interferon Type I; C439669:interferon kappa
Common variable immunodeficiency (CVID); Interferon kappa gene (IFNK); Whole exome sequencing