PDF(Pubmed)
Abstract：
Glutaric aciduria type 1 (GA-1) is a rare but treatable autosomal-recessive neurometabolic disorder of lysin metabolism caused by biallelic pathogenic variants in glutaryl-CoA dehydrogenase gene (GCDH) that lead to deficiency of GCDH protein. Without treatment, this enzyme defect causes a neurological phenotype characterized by movement disorder and cognitive impairment. Based on a comprehensive literature search, we established a large dataset of GCDH variants using the Leiden Open Variation Database (LOVD) to summarize the known genotypes and the clinical and biochemical phenotypes associated with GA-1. With these data, we developed a GCDH-specific variation classification framework based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. We used this framework to reclassify published variants and to describe their geographic distribution, both of which have practical implications for the molecular genetic diagnosis of GA-1. The freely available GCDH-specific LOVD dataset provides a basis for diagnostic laboratories and researchers to further optimize their knowledge and molecular diagnosis of this rare disease.
摘要：
戊二酸尿症1型（GA-1）是一种罕见但可治疗的常染色体隐性神经代谢疾病，由戊二酰辅酶A脱氢酶基因（GCDH）的双等位基因致病变异引起，导致GCDH蛋白缺乏。如果没有治疗,这种酶缺陷导致以运动障碍和认知障碍为特征的神经表型。在全面文献检索的基础上，我们使用莱顿开放变异数据库(LOVD)建立了GCDH变异的大型数据集,以总结已知基因型以及与GA-1相关的临床和生化表型.有了这些数据,我们基于美国医学遗传学和基因组学学院和分子病理学协会指南,开发了GCDH特异性变异分类框架.我们使用这个框架来重新分类已发布的变体并描述它们的地理分布，两者都对GA-1的分子遗传学诊断具有实际意义。免费提供的GCDH特异性LOVD数据集为诊断实验室和研究人员进一步优化他们对这种罕见疾病的知识和分子诊断提供了基础。
