Section of Colon and Rectal Surgery, Creighton University School of Medicine/CHI Medical Center, Omaha, NE, United States.
Section of Colon and Rectal Surgery, Creighton University School of Medicine/CHI Medical Center, Omaha, NE, United States.
Am J Surg. 2018 Dec;216(6):1148-1154. doi: 10.1016/j.amjsurg.2018.08.008. Epub 2018 Sep 7.
Genetic variants of unknown significance (VUS) are an increasingly common result of genetic testing. VUS present dilemmas for treatment and surveillance. Family history may play a role in VUS reclassification over time.
All genetic tests performed at a tertiary referral center 2006-2015 were evaluated for the presence of VUS. Patients with VUS were evaluated for demographics, clinical characteristics, family history, and gene characteristics.
In total, 2291 individuals were tested from 1639 families; 150 VUS were identified. Twenty-eight VUS reclassified, 21 to benign and 7 to pathogenic. Logistic regression demonstrated the number of family members with associated phenotypic disease was a significant predictor of reclassification.
The likelihood of VUS reclassification can be predicted by increased positive family history of disease. Most VUS reclassify to benign, but one-fourth reclassify to pathogenic. The actual risk of a VUS should be assessed based on family history and routinely checked for reclassification.
未明意义的遗传变异（VUS）是遗传检测中越来越常见的结果。VUS 给治疗和监测带来了困境。随着时间的推移，家族史可能在 VUS 的重新分类中发挥作用。
评估了 2006 年至 2015 年在三级转诊中心进行的所有基因检测中是否存在 VUS。对 VUS 患者进行了人口统计学、临床特征、家族史和基因特征评估。
共对 1639 个家族的 2291 人进行了检测，发现 150 个 VUS。28 个 VUS 重新分类，21 个为良性，7 个为致病性。逻辑回归表明，具有相关表型疾病的家族成员数量是重新分类的重要预测因素。
疾病阳性家族史增加可预测 VUS 的重新分类。大多数 VUS 重新分类为良性，但四分之一重新分类为致病性。VUS 的实际风险应根据家族史进行评估，并定期进行重新分类检查。
