Loss-of-function variants in SAT1 cause X-linked childhood-onset systemic lupus erythematosus.

ABSTRACT:

Objectives

Families that contain multiple siblings affected with childhood onset of systemic lupus erythematosus (SLE) likely have strong genetic predispositions. We performed whole exome sequencing (WES) to identify familial rare risk variants and to assess their effects in lupus.

Methods

Sanger sequencing validated the two ultra-rare, predicted pathogenic risk variants discovered by WES and identified additional variants in 562 additional patients with SLE. Effects of a splice site variant and a frameshift variant were assessed using a Minigene assay and CRISPR/Cas9-mediated knock-in (KI) mice, respectively.

Results

The two familial ultra-rare, predicted loss-of-function (LOF) SAT1 variants exhibited X-linked recessive Mendelian inheritance in two unrelated A

SUBMITTER: Xu L 

PROVIDER: S-EPMC10394691 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature