Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing

Abstract

The genetics underlying non-syndromic familial non-medullary thyroid carcinoma (FNMTC) is still poorly understood. To identify susceptibility genes for FNMTC, we performed whole-exome sequencing (WES) in a Brazilian family affected by papilla ry thyroid carcinoma (PTC) in three consecutive generations. WES was performed in four affe cted and two unaffected family members. Manual inspection in over 100 previously reported susceptibility genes for FNMTC showed that no variants in known genes co-segregated with disease phenotype in this family. Novel candidate genes were investigated using PhenoDB and filtered using Genome Aggregation (gnomAD) and Online Archive of Brazilian Mutations (ABraOM) population databases. The missense variant p.Ile657Met in the NID1 gene was the only variant that co-segregated with the disease, while abs ent in unaffected family members and controls. The allele frequency for this variant was G) identified in this study fulfills several criteria th at suggest it as a new FNMTC predisposing gene.

Keywords

• nid1
• fnmtc
• papillary thyroid carcinomas
• whole-exome sequencing