|Title||A potential founder variant in CARMIL2/RLTPR in three Norwegian families with warts, molluscum contagiosum, and T-cell dysfunction.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Sorte, HS, Osnes, LT, Fevang, B, Aukrust, P, Erichsen, HC, Backe, PH, Abrahamsen, TG, Kittang, OB, Øverland, T, Jhangiani, SN, Muzny, DM, Vigeland, MD, Samarakoon, P, Gambin, T, Akdemir, ZHC, Gibbs, RA, Rødningen, OK, Lyle, R, Lupski, JR, Stray-Pedersen, A|
|Journal||Mol Genet Genomic Med|
|Date Published||2016 Nov|
BACKGROUND: Four patients from three Norwegian families presented with a common skin phenotype of warts, molluscum contagiosum, and dermatitis since early childhood, and various other immunological features. Warts are a common manifestation of human papilloma virus (HPV), but when they are overwhelming, disseminated and/or persistent, and presenting together with other immunological features, a primary immunodeficiency disease (PIDD) may be suspected.
METHODS AND RESULTS: The four patients were exome sequenced as part of a larger study for detecting genetic causes of primary immunodeficiencies. No disease-causing variants were identified in known primary immunodeficiency genes or in other disease-related OMIM genes. However, the same homozygous missense variant in CARMIL2 (also known as RLTPR) was identified in all four patients. In each family, the variant was located within a narrow region of homozygosity, representing a potential region of autozygosity. CARMIL2 is a protein of undetermined function. A role in T-cell activation has been suggested and the mouse protein homolog (Rltpr) is essential for costimulation of T-cell activation via CD28, and for the development of regulatory T cells. Immunophenotyping demonstrated reduced regulatory, CD4+ memory, and CD4+ follicular T cells in all four patients. In addition, they all seem to have a deficiency in IFN γ -synthesis in CD4+ T cells and NK cells.
CONCLUSIONS: We report a novel primary immunodeficiency, and a differential molecular diagnosis to CXCR4-,DOCK8-,GATA2-,MAGT1-,MCM4-,STK4-,RHOH-,TMC6-, and TMC8-related diseases. The specific variant may represent a Norwegian founder variant segregating on a population-specific haplotype.
|Alternate Journal||Mol Genet Genomic Med|
|PubMed Central ID||PMC5118205|