Hutchcraft Megan Leigh, Zhang Shulin, Lin Nan, Gottschalk Ginny Lee, Keck James W, Belcher Elizabeth A, Sears Catherine, Wang Chi, Liu Kun, Dietz Lauren E, Pickarski Justine C, Wei Sainan, Cardarelli Roberto, DiPaola Robert S, Kolesar Jill M
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Kentucky Markey Cancer Center, Lexington, KY 40536, USA.
Department of Pathology and Laboratory Medicine, University of Kentucky Chandler Medical Center, Lexington, KY 40536, USA.
J Pers Med. 2022 Aug 8;12(8):1297. doi: 10.3390/jpm12081297.
Hereditary factors contribute to disease development and drug pharmacokinetics. The risk of hereditary disease development can be attenuated or eliminated by early screening or risk reducing interventions. The purpose of this study was to assess the clinical utility of germline medical exome sequencing in patients recruited from a family medicine clinic and compare the mutation frequency of hereditary predisposition genes to established general population frequencies. At the University of Kentucky, 205 family medicine patients underwent sequencing in a Clinical Laboratory Improvement Amendments of 1988-compliant laboratory to identify clinically actionable genomic findings. The study identified pathogenic or likely pathogenic genetic variants-classified according to the American College of Medical Genetics and Genomics variant classification guidelines-and actionable pharmacogenomic variants, as defined by the Clinical Pharmacogenetics Implementation Consortium. Test results for patients with pharmacogenomic variants and pathogenic or likely pathogenic variants were returned to the participant and enrolling physician. Hereditary disease predisposition gene mutations in , , , , , , , , or were identified in 6.3% (13/205) of the patients. Nine of 13 (69.2%) underwent subsequent clinical interventions. Pharmacogenomic variants were identified in 76.1% (156/205) of patients and included 4.9% (10/205) who were prescribed a medication that had pharmacogenomic implications. Family physicians changed medications for 1.5% (3/205) of patients to prevent toxicity. In this pilot study, we found that with systemic support, germline genetic screening initiatives were feasible and clinically beneficial in a primary care setting.
遗传因素对疾病发展和药物药代动力学有影响。通过早期筛查或降低风险的干预措施，可以减轻或消除遗传性疾病发展的风险。本研究的目的是评估从家庭医学诊所招募的患者中种系医学外显子测序的临床实用性，并将遗传性易感性基因的突变频率与既定的一般人群频率进行比较。在肯塔基大学，205名家庭医学患者在符合1988年《临床实验室改进修正案》的实验室中进行了测序，以确定具有临床可操作性的基因组发现。该研究确定了根据美国医学遗传学与基因组学学会变异分类指南分类的致病性或可能致病性基因变异，以及临床药物基因组学实施联盟定义的可操作药物基因组学变异。将具有药物基因组学变异以及致病性或可能致病性变异患者的检测结果反馈给参与者和参与的医生。在6.3%（13/205）的患者中发现了、、、、、、、或中的遗传性疾病易感性基因突变。13名患者中有9名（69.2%）随后接受了临床干预。在76.1%（156/205）的患者中发现了药物基因组学变异，其中4.9%（10/205）的患者被开具了具有药物基因组学意义的药物。家庭医生为1.5%（3/205）的患者更换了药物以预防毒性。在这项初步研究中，我们发现，在系统支持下，种系基因筛查计划在初级保健环境中是可行的且具有临床益处。
