Novel FTA2 variants were observed in patients with restless legs syndrome via whole-exome sequencing

Background: Restless legs syndrome (RLS) is often characterized by familial aggregation. Molecular genetic changes are closely related to the occurrence of the disease, but the key gene variations are unclear. Here, genetic changes were investigated in an RLS family. Methods: 4 ml EDTA anticoagulant peripheral blood was collected from patients in a family with RLS, and genomic DNA was extracted. Whole-exome sequencing (WES) was performed by the Illumina platform, and variants were distinguished by GATK haplotype caller software. Polyphen-2 and SIFT tools were used to analyze the effect of missense mutations on protein structure and function, and the HSF tool was used to analyze the effect of variants on splicing defects. Results: Based on the RLS diagnostic criteria, 4 individuals were diagnosed with RLS in this family. Among them, three subjects underwent a WES examination, and two novel FAT2 variants were detected in all subjects: exon 6:c.4174g > A, p.Asp1392Asn and intron 19: c.11464-8C > G. The frequency of these two variants was extremely rare in the normal population database. Polyphen2 tool analysis results suggested c.4174G> A, p.Asp1392Asn, was identified as probably damaging with a 0.910 score (sensitivity: 0.69; specificity: 0.90); SIFT tool predicts that its risk factor score is −1.510 (＞ 2.5), which is considered neutral damage. For intron19: c.11464-8C > G,, although mutation occurred in the late intron position, no obvious splicing sequence change was predicted by the HSF software. Conclusion: Two novel FAT2 variants were identified in three patients from an RLS family, of which exon 6: c.4174G > A was likely to damage protein function.