Genetic cause of immune dysregulation - one gene or two?
Some autoimmune disorders are monogenetic diseases; however, clinical manifestations among individuals vary, despite the presence of identical mutations in the disease-causing gene. In this issue of the JCI, Massaad and colleagues characterized a seemingly monogenic autoimmune disorder in a family that was linked to homozygous loss-of-function mutations in the gene encoding the endonuclease Nei endonuclease VIII-like 3 (NEIL3), which has not been previously associated with autoimmunity. The identification of an unrelated healthy individual with the same homozygous mutation spurred more in-depth analysis of the data and revealed the presence of a second mutation in a known autoimmune-associated gene. Animals lacking Neil3 had no overt phenotype, but were predisposed to autoantibody production and nephritis following exposure to the TLR3 ligand poly(I:C). Together, these results support further evaluation of the drivers of autoimmunity in supposedly monogenic disorders.
|Authors||Tangye, S. G.|
|Responsible Garvan Author|
|Publisher Name||JOURNAL OF CLINICAL INVESTIGATION|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/27760052|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/13527|