Cornélis François
Clinical Genetics Unit, Rheumatology Federation, Lariboisière Teaching Hospital, 2, rue Ambroise-Paré, 75010 Paris, France.
Joint Bone Spine. 2003 Dec;70(6):458-64. doi: 10.1016/j.jbspin.2003.09.005.
The dramatic advances made recently in human genome research are fueling considerable interest in genetic testing. A specific feature of genetic testing is that the results are final and impact not only the patient, but also the entire family. Those elements should be factored into the risk/benefit ratio evaluation. In France, legislation the differentiates diagnostic tests in symptomatic patients from predictive tests in asymptomatic patients with affected family members. Only multidisciplinary groups with both clinical and genetic expertise can order predictive tests. In all cases the physician must sign a statement that informed consent was obtained from the patient prior to testing. The test must be done in an accredited laboratory and the result communicated by the physician to the patient. Patient confidentiality must be respected, particularly regarding family members. In monogenic diseases, the diagnostic weight of genetic testing is often considerable, although the limitations should be borne in mind. In multifactorial diseases, genetic testing seeks to identify risk factors that are usually associated with a low level of risk. The result should be interpreted in the light of the clinical presentation, family history, and genetic background. The predictive value is closely dependent on the clinical presentation but is generally limited, most notably when family members are affected. Great care should be taken to avoid causing undue anxiety among individuals with positive test results. Diseases that illustrate these aspects include Paget's disease of bone, of which inherited variants caused by a mutation in a single gene on chromosome 5 have been identified recently, and rheumatoid arthritis, which is a multifactorial disease.
人类基因组研究最近取得的巨大进展引发了人们对基因检测的浓厚兴趣。基因检测的一个特点是其结果是最终的，不仅会影响患者，还会影响整个家庭。在评估风险/收益比时应考虑这些因素。在法国，立法将有症状患者的诊断性检测与有患病家庭成员的无症状患者的预测性检测区分开来。只有具备临床和基因专业知识的多学科团队才能开具预测性检测的医嘱。在所有情况下，医生必须签署一份声明，表明在检测前已获得患者的知情同意。检测必须在经认可的实验室进行，结果由医生告知患者。必须尊重患者的隐私，尤其是涉及家庭成员的隐私。在单基因疾病中，基因检测的诊断权重通常很大，不过也应牢记其局限性。在多因素疾病中，基因检测旨在识别通常与低风险水平相关的风险因素。结果应根据临床表现、家族史和基因背景来解读。预测价值很大程度上取决于临床表现，但通常有限，在家庭成员患病的情况下尤其如此。应格外小心，避免给检测结果呈阳性的个体带来不必要的焦虑。能说明这些情况的疾病包括骨佩吉特病，最近已发现其由5号染色体上单个基因突变引起的遗传变异，以及类风湿关节炎，它是一种多因素疾病。
