Background: Nonmedullary thyroid cancer (NMTC) comprises approximately 90% of all thyroid cancers, and about 3% to 9% of NMTC cases have a familial origin. Familial NMTC (FNMTC) in the absence of a documented familial cancer syndrome such as Cowden syndrome is characterized by the occurrence of thyroid cancer of follicular cell origin in 2 or more first-degree relatives.
Methods: Whole-exome sequencing (WES) was used to identify pathogenic genetic variants in 2 Persian families with FNMTC. The purpose of this work is to assess the pathogenic status of these variants as well as the cosegregation status of the variants observed in the examined families.
Results: By analyzing WES data in the first family, SRGAP1: NM_020762: exon16: c.C1849T was identified as a pathogenic variant. This variant was confirmed by Sanger sequencing. In the second family, the variant FOXE1: NM_004473: exon1: c.531_532insCGCGA was identified but was not confirmed by Sanger sequencing.
Conclusion: Based on the data, SRGAP1 can be a potential candidate gene for susceptibility to FNMTC in the first family. However, additional analyses like whole genome sequencing and copy number variations are required to ascertain the disease status in second family.
Keywords: FOXE1; SRGAP1; cancer; familial; nonmedullary; thyroid; whole-exome sequencing.
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