French Referral Center for Fabry disease, Division of Medical Genetics, University of Versailles, Montigny, France.
First Faculty of Medicine, Charles University, Prague, Czech Republic.
Mol Genet Genomic Med. 2021 May;9(5):e1666. doi: 10.1002/mgg3.1666. Epub 2021 Apr 9.
Family genetic testing of patients newly diagnosed with a rare genetic disease can improve early diagnosis of family members, allowing patients to receive disease-specific therapies when available. Fabry disease, an X-linked lysosomal storage disorder caused by pathogenic variants in GLA, can lead to end-stage renal disease, cardiac arrhythmias, and stroke. Diagnostic delays are common due to the rarity of the disease and non-specificity of early symptoms. Newborn screening and screening of at-risk populations, (e.g., patients with hypertrophic cardiomyopathy or undiagnosed nephropathies) can identify individuals with Fabry disease. Subsequent cascade genotyping of family members may disclose a greater number of affected individuals, often at younger age than they would have been diagnosed otherwise.
We conducted a literature search to identify all published data on family genetic testing for Fabry disease, and discussed these data, experts' own experiences with family genetic testing, and the barriers to this type of screening that are present in their respective countries.
There are potential barriers that make implementation of family genetic testing challenging in some countries. These include associated costs and low awareness of its importance, and cultural and societal issues. Regionally, there are barriers associated with population educational levels, national geography and infrastructures, and a lack of medical geneticists.
In this review, the worldwide experience of an international group of experts of Fabry disease highlights the issues faced in the family genetic testing of patients affected with rare genetic diseases.
对新诊断出罕见遗传性疾病的患者进行家系基因检测，可改善家庭成员的早期诊断，使患者在有条件时能获得针对该病的治疗。由于 GLA 中的致病性变异引起的 X 连锁溶酶体贮积症——法布瑞病，可导致终末期肾病、心律失常和中风。由于该病罕见且早期症状缺乏特异性，故常会出现诊断延迟。通过新生儿筛查和高危人群（例如肥厚型心肌病或未确诊的肾脏病患者）筛查，可发现法布瑞病患者。随后对家系成员进行级联基因分型，可能会发现更多的受影响个体，通常比未接受基因筛查的个体更早被诊断。
我们进行了文献检索，以确定所有已发表的关于法布瑞病家系基因检测的资料，并讨论了这些资料、专家自身在法布瑞病家系基因检测方面的经验，以及各自国家中存在的此类筛查障碍。
在某些国家，实施家系基因检测存在潜在障碍。这些障碍包括相关费用和对其重要性认识不足，以及文化和社会问题。在区域层面，还存在与人口教育水平、国家地理和基础设施以及缺乏医学遗传学家相关的障碍。
在本综述中，一组国际法布瑞病专家的全球经验突出了在患有罕见遗传性疾病的患者中进行家系基因检测所面临的问题。
