Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：非甲状腺髓样癌（NMTC）约占所有甲状腺癌的90％，约3％至9％的NMTC病例具有家族起源。家族性NMTC(FNMTC)在没有文献记载的家族性癌症综合征例如Cowden综合征的情况下,其特征在于在2个或更多个一级亲属中发生滤泡细胞起源的甲状腺癌。
方法：使用全外显子组测序（WES）鉴定2个FNMTC波斯家族的致病遗传变异。这项工作的目的是评估这些变体的致病状态以及在所检查的家族中观察到的变体的共分离状态。
结果：通过分析第一家族的WES数据，SRGAP1:NM_020762:exon16:c.C1849T被鉴定为致病变体。通过Sanger测序证实了该变体。在第二个家庭，鉴定出变体FOXE1:NM_004473:外显子1:c.531_532insCGCGA,但未通过Sanger测序证实。
结论：根据数据，SRGAP1可能是第一家族中FNMTC易感性的潜在候选基因。然而,需要进行其他分析，例如全基因组测序和拷贝数变异，以确定第二家族的疾病状况。
方法：使用全外显子组测序（WES）鉴定2个FNMTC波斯家族的致病遗传变异。这项工作的目的是评估这些变体的致病状态以及在所检查的家族中观察到的变体的共分离状态。
结果：通过分析第一家族的WES数据，SRGAP1:NM_020762:exon16:c.C1849T被鉴定为致病变体。通过Sanger测序证实了该变体。在第二个家庭，鉴定出变体FOXE1:NM_004473:外显子1:c.531_532insCGCGA,但未通过Sanger测序证实。
结论：根据数据，SRGAP1可能是第一家族中FNMTC易感性的潜在候选基因。然而,需要进行其他分析，例如全基因组测序和拷贝数变异，以确定第二家族的疾病状况。
