International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.
International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.
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DOI：
10.1016/j.ajhg.2017.04.003
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发表时间：
2017-05-04
影响因子：
9.8
通讯作者：
Lochmüller H
中科院分区：
文献类型：
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作者：
Boycott KM;Rath A;Chong JX;Hartley T;Alkuraya FS;Baynam G;Brookes AJ;Brudno M;Carracedo A;den Dunnen JT;Dyke SOM;Estivill X;Goldblatt J;Gonthier C;Groft SC;Gut I;Hamosh A;Hieter P;Höhn S;Hurles ME;Kaufmann P;Knoppers BM;Krischer JP;Macek M Jr;Matthijs G;Olry A;Parker S;Paschall J;Philippakis AA;Rehm HL;Robinson PN;Sham PC;Stefanov R;Taruscio D;Unni D;Vanstone MR;Zhang F;Brunner H;Bamshad MJ;Lochmüller H
及时为患有罕见遗传病的儿童和成人提供分子确诊，缩短了他们的“诊断历程”，改善了疾病管理，并促进了关于复发风险的遗传咨询，同时确保生殖选择。在一般的临床遗传学背景下，目前的诊断率约为50%，但对于那些在最初的遗传学评估后没有接受分子诊断的人来说，这一比率要低得多。对这些更具挑战性的受影响个体的诊断成功在很大程度上取决于发现与罕见疾病相关的基因和机制的进展。因此，需要继续研究，以走向更完整的疾病相关基因和变异的目录。国际罕见病研究联盟（IRDiRC）成立于2011年，旨在将投资于罕见病研究的研究人员和组织聚集在一起，以开发实现所有罕见病分子诊断的方法。在这里，我们回顾了基因发现当前和未来的瓶颈，并提出了实现这方面进展的策略。每一项成功的发现都将为相应的罕见疾病定义潜在的诊断、预防和治疗机会，从而为这一患者群体提供精准医疗。
Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their “diagnostic odyssey,” improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases. Thus, continued research is required for moving toward a more complete catalog of disease-related genes and variants. The International Rare Diseases Research Consortium (IRDiRC) was established in 2011 to bring together researchers and organizations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. Here, we review the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. Each successful discovery will define potential diagnostic, preventive, and therapeutic opportunities for the corresponding rare disease, enabling precision medicine for this patient population.