Unknown

Dataset Information

0

Dominant-negative loss of function arises from a second, more frequent variant within the SAND domain of autoimmune regulator (AIRE).


ABSTRACT: A genetic variant in the SAND domain of autoimmune regulator (AIRE), R247C, was identified in a patient with type I diabetes mellitus (T1DM) and his mother with rheumatoid arthritis. In vitro, the variant dominantly inhibited AIRE; however, typical features of Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECED) were not seen in the subjects. Rather, early manifestation of autoimmunity appeared to be dependent on additional genetic factors. On a population level, diverse variants were identified in this region. Surprisingly, many likely pathogenic variants were seen disproportionately in Africans when compared to Europeans, reinforcing the importance of these variants in altering the immune repertoire. In light of these findings, we propose that R247C and other variants within the SAND-domain alter protein function in a dominant fashion and hold potential as drivers of autoimmunity.

SUBMITTER: Abbott JK 

PROVIDER: S-EPMC5846191 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

Dominant-negative loss of function arises from a second, more frequent variant within the SAND domain of autoimmune regulator (AIRE).

Abbott Jordan K JK   Huoh Yu-San YS   Reynolds Paul R PR   Yu Liping L   Rewers Marian M   Reddy Monica M   Anderson Mark S MS   Hur Sun S   Gelfand Erwin W EW  

Journal of autoimmunity 20171110


A genetic variant in the SAND domain of autoimmune regulator (AIRE), R247C, was identified in a patient with type I diabetes mellitus (T1DM) and his mother with rheumatoid arthritis. In vitro, the variant dominantly inhibited AIRE; however, typical features of Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECED) were not seen in the subjects. Rather, early manifestation of autoimmunity appeared to be dependent on additional genetic factors. On a population level, diverse v  ...[more]

Similar Datasets

| S-EPMC7521301 | biostudies-literature
| S-EPMC10206195 | biostudies-literature
| S-EPMC5016183 | biostudies-other
| S-EPMC5976627 | biostudies-literature
| S-EPMC6351566 | biostudies-literature
| S-EPMC7039057 | biostudies-literature
| S-EPMC3145727 | biostudies-literature
2016-06-14 | PXD002511 | Pride
| S-EPMC7339480 | biostudies-literature
| S-EPMC8421262 | biostudies-literature