Familial non medullary thyroid cancer:a case series in Iranian patients with a meta-review of caseseries

Introduction: Non-medullary thyroid cancer (NMTC) comprisesapproximately ۹۰% of all thyroid cancers, and about۳–۹% of NMTC cases have a familial origin. Familial nonmedullarythyroid cancer (FNMTC) in the absence of a documentedfamilial cancer syndrome such as Cowden syndrome orfamilial adenomatous polyposis is characterized by the occurrenceof thyroid cancer of follicular cell origin in two or morefirst-degree relatives. However, the genes responsible for thenon-syndromic type of FNMTC are still poorly understood. Inthis study, WES was used to identify pathogenic genetic variantsin two Persian families with FNMTC. The purpose of thiswork is to assess the pathogenic status of these variants as wellas the co-segregation status of the variants observed in the examinedfamilies.Methods: Whole-Exome Sequencing (WES) was conductedon DNA taken from a blood sample of two probands from twoIranian families with papillary thyroid cancer to find probablecausal variants. The pathogenicity of the potential variants wasthen assessed using in-silico tools, and Sanger sequencing wasfinally employed to confirm these variants and carry out cosegregationstudies.Results: By analyzing WES data in the first family, SRGAP۱:NM_۰۲۰۷۶۲: exon۱۶: c.C۱۸۴۹T, was identified as a pathogenicvariant. This variant was confirmed by Sanger sequencing, andthe presence of a carrier of this variant was identified in thisfamily. In the second family, the variant FOXE۱: NM_۰۰۴۴۷۳:exon۱: c.۵۳۱_۵۳۲insCGCGA was identified. This variant is anew type of frameshift insertion that was not previously reportedbut was not confirmed by Sanger sequencing.Conclusion: Based on these data, SRGAP۱ can be a potentialcandidate gene for susceptibility to FNMTC in the first family.However, additional analyses like whole-genome sequencing(WGS) and copy number variations (CNV) are required to ascertainthe disease status in the second family

کلیدواژه ها:

Familial non-medullary thyroid cancer ، Whole-exomesequencing ، SRGAP۱ ، FOXE۱