长期以来，人们一直观察到存在非髓样甲状腺癌（NMTC）发生的家族，但迄今为止描述的综合征和基因很少。庇护蛋白复合物中的蛋白质与癌症有关。在这里，我们研究了受 NMTC (FNMTC) 影响的家庭中的庇护蛋白基因。我们对来自 4 个家庭（至少有 3 名受影响成员）的 10 名受影响个体进行了全外显子组测序 (WES)。通过聚合酶链式反应 (PCR) 和 Sanger 测序来寻找 40 个 FNMTC 家族中 TINF2 基因的变异。在一个家族的几名受影响患者中研究了 TINF2 转录本和杂合性丢失 (LOH)。我们在一个家族的 TINF2 基因中发现杂合性 c.507G>T 变异，在所有五个受影响成员中共分离。这种变异会影响正常的剪接。未观察到 LOH。我们的结果强化了 TINF2 基因作为 FNMTC 易感性的原因，表明移码变异在 TINF2 中定位的重要性。根据我们的数据和之前的文献，TINF2 致病性变异似乎是 NMTC 和/或黑色素瘤发展的重要风险因素。© 作者（或其雇主）2024。禁止商业重复使用。请参阅权利和权限。英国医学杂志出版。

It has long been observed that there are families in which non-medullary thyroid cancer (NMTC) occurs, but few syndromes and genes have been described to date. Proteins in the shelterin complex have been implied in cancer. Here, we have studied shelterin genes in families affected by NMTC (FNMTC).We performed whole-exome sequencing (WES) in 10 affected individuals from four families with at least three affected members. Polymerase chain reaction (PCR) and Sanger sequencing were performed to search for variants in the TINF2 gene in 40 FNMTC families. TINF2 transcripts and loss of heterozygosity (LOH) were studied in several affected patients of one family.We found the c.507G>T variant in heterozygosis in the TINF2 gene in one family, co-segregating in all five affected members. This variant affects the normal splicing. LOH was not observed.Our results reinforce the TINF2 gene as a susceptibility cause of FNMTC suggesting the importance of location of frameshift variants in TINF2. According to our data and previous literature, TINF2 pathogenic variants appear to be a significant risk factor for the development of NMTC and/or melanoma.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.