PDF(Pubmed)
Abstract：
BACKGROUND: Despite the efforts that have been made to standardize the interpretation of variants, in some cases, their pathogenicity remains vague and confusing, and sometimes their interpretation does not help clinicians to establish clinical correlation using genetic test results. This study aims to shed more lights on these challenging variants.
METHODS: In a clinical setting, the variants found from 81 array CGH and 79 whole exome sequencing (WES) in patients with congenital anomalies were interpreted based on American College of Medical Genetics and Genomics guidelines.
RESULTS: In this study, the interpretation of the disease-causing variants and the variants with uncertain clinical significance detected by WES was far more challenging than the variants detected by array CGH. The presence of unreported clinical symptoms, incomplete penetrance, variable expressivity, parents\' reluctance to analyze segregation in the family, and the limitations of prenatal tests, were among the challenging factors in the interpretation of variants in this study.
CONCLUSIONS: A careful study of the pedigree and disease mode of inheritance, as well as a careful clinical examination of the carrier parents in diseases with autosomal dominant inheritance, are among the primary strategies for determining the clinical significance of the variants. Continued efforts to mitigate these challenges are needed to improve the interpretation of variants.
METHODS: In a clinical setting, the variants found from 81 array CGH and 79 whole exome sequencing (WES) in patients with congenital anomalies were interpreted based on American College of Medical Genetics and Genomics guidelines.
RESULTS: In this study, the interpretation of the disease-causing variants and the variants with uncertain clinical significance detected by WES was far more challenging than the variants detected by array CGH. The presence of unreported clinical symptoms, incomplete penetrance, variable expressivity, parents\' reluctance to analyze segregation in the family, and the limitations of prenatal tests, were among the challenging factors in the interpretation of variants in this study.
CONCLUSIONS: A careful study of the pedigree and disease mode of inheritance, as well as a careful clinical examination of the carrier parents in diseases with autosomal dominant inheritance, are among the primary strategies for determining the clinical significance of the variants. Continued efforts to mitigate these challenges are needed to improve the interpretation of variants.
摘要：
背景：尽管已经为标准化变体的解释做出了努力，在某些情况下,它们的致病性仍然模糊和令人困惑，有时它们的解释并不能帮助临床医生使用基因检测结果建立临床相关性。这项研究旨在为这些具有挑战性的变种提供更多的启示。
方法：在临床环境中，根据美国医学遗传学和基因组学学会指南对先天性异常患者的81阵列CGH和79个全外显子组测序(WES)中发现的变异进行了解释.
结果：在这项研究中，对由WES检测到的致病变异体和具有不确定临床意义的变异体的解释远比由阵列CGH检测到的变异体更具挑战性.存在未报告的临床症状，不完整的外显率,可变的表现力，父母不愿分析家庭中的种族隔离，以及产前检查的局限性，是本研究中解释变体的挑战性因素之一。
结论：对遗传的谱系和疾病模式进行仔细研究，以及在常染色体显性遗传的疾病中对携带者父母进行仔细的临床检查，是确定变异的临床意义的主要策略之一。需要继续努力减轻这些挑战，以改进对变体的解释。
方法：在临床环境中，根据美国医学遗传学和基因组学学会指南对先天性异常患者的81阵列CGH和79个全外显子组测序(WES)中发现的变异进行了解释.
结果：在这项研究中，对由WES检测到的致病变异体和具有不确定临床意义的变异体的解释远比由阵列CGH检测到的变异体更具挑战性.存在未报告的临床症状，不完整的外显率,可变的表现力，父母不愿分析家庭中的种族隔离，以及产前检查的局限性，是本研究中解释变体的挑战性因素之一。
结论：对遗传的谱系和疾病模式进行仔细研究，以及在常染色体显性遗传的疾病中对携带者父母进行仔细的临床检查，是确定变异的临床意义的主要策略之一。需要继续努力减轻这些挑战，以改进对变体的解释。
