Lanthaler Barbara, Wieser Stefanie, Deutschmann Andrea, Schossig Anna, Fauth Christine, Zschocke Johannes, Witsch-Baumgartner Martina
Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.
Department of Paediatrics and Adolescent Medicine, Hospital Salzburg, Salzburg, Austria.
Gene. 2014 Oct 15;550(1):136-40. doi: 10.1016/j.gene.2014.08.016. Epub 2014 Aug 8.
Inherited diseases are the result of DNA sequence changes. In recessive diseases, the clinical phenotype results from the combined functional effects of variants in both copies of the gene. In some diseases there is often considerable variability of clinical presentation or disease severity, which may be predicted by the genotype. Additional effects may be triggered by environmental factors, as well as genetic modifiers which could be nucleotide polymorphisms in related genes, e.g. maternal ApoE or ABCA1 genotypes which may have an influence on the phenotype of SLOS individuals. Here we report the establishment of genotype variation databases for various rare diseases which provide individual clinical phenotypes associated with genotypes and include data about possible genetic modifiers. These databases aim to be an easy public access to information on rare and private variants with clinical data, which will facilitate the interpretation of genetic variants. The created databases include ACAD8 (isobutyryl-CoA dehydrogenase deficiency (IBD)), ACADSB (short-chain acyl-CoA dehydrogenase (SCAD) deficiency), AUH (3-methylglutaconic aciduria (3-MGCA)), DHCR7 (Smith-Lemli-Opitz syndrome), HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency), HSD17B10 (17-beta-hydroxysteroid dehydrogenase X deficiency), FKBP14 (Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss; EDSKMH) and ROGDI (Kohlschütter-Tönz syndrome). These genes have been selected because of our specific research interests in these rare and metabolic diseases. The aim of the database was to include all identified individuals with variants in these specific genes. Identical genotypes are listed multiple times if they were found in several patients, phenotypic descriptions and biochemical data are included as detailed as possible in view also of validating the proposed pathogenicity of these genotypes. For DHCR7 genetic modifier data (maternal APOE and ABCA1 genotypes) is also included. Databases are available at http://databases.lovd.nl/shared/genes and will be updated based on periodic literature reviews and submitted reports.
遗传性疾病是DNA序列变化的结果。在隐性疾病中，临床表型是由基因两个拷贝中变异的综合功能效应导致的。在某些疾病中，临床表现或疾病严重程度往往存在相当大的变异性，这可能由基因型预测。环境因素以及遗传修饰因子可能会引发额外的效应，遗传修饰因子可能是相关基因中的核苷酸多态性，例如母亲的载脂蛋白E或ABCA1基因型，它们可能会影响史密斯-勒米-奥皮茨综合征（SLOS）患者的表型。在此，我们报告了针对各种罕见疾病建立的基因型变异数据库，这些数据库提供了与基因型相关的个体临床表型，并包含有关可能的遗传修饰因子的数据。这些数据库旨在方便公众轻松获取有关罕见和私人变异以及临床数据的信息，这将有助于对基因变异进行解读。创建的数据库包括ACAD8（异丁酰辅酶A脱氢酶缺乏症（IBD））、ACADSB（短链酰基辅酶A脱氢酶（SCAD）缺乏症）、AUH（3-甲基戊二酸尿症（3-MGCA））、DHCR7（史密斯-勒米-奥皮茨综合征）、HMGCS2（3-羟基-3-甲基戊二酰辅酶A合酶2缺乏症）、HSD17B10（17-β-羟基类固醇脱氢酶X缺乏症）、FKBP14（伴有进行性脊柱后凸、肌病和听力丧失的埃勒斯-当洛综合征；EDSKMH）和ROGDI（科尔施许特-滕茨综合征）。选择这些基因是因为我们对这些罕见和代谢性疾病有特定的研究兴趣。该数据库的目的是纳入所有在这些特定基因中发现变异的个体。如果在多名患者中发现相同的基因型，则会多次列出，同时会尽可能详细地纳入表型描述和生化数据，以便也能验证这些基因型的假定致病性。对于DHCR7，还纳入了遗传修饰因子数据（母亲的APOE和ABCA1基因型）。数据库可在http://databases.lovd.nl/shared/genes获取，并将根据定期的文献综述和提交的报告进行更新。
