Institute of Human Genetics, University of Leipzig Medical Center, Philipp-Rosenthal-Straße 55, 04103 Leipzig, Germany.
Genes (Basel). 2022 Dec 7;13(12):2305. doi: 10.3390/genes13122305.
Routine diagnostics is biased towards genes and variants with satisfactory evidence, but rare disorders with only little confirmation of their pathogenicity might be missed. Many of these genes can, however, be considered relevant, although they may have less evidence because they lack OMIM entries or comprise only a small number of publicly available variants from one or a few studies. Here, we present 89 individuals harbouring variants in 77 genes for which only a small amount of public evidence on their clinical significance is available but which we still found to be relevant enough to be reported in routine diagnostics. For 21 genes, we present case reports that confirm the lack or provisionality of OMIM associations (), broaden the phenotypic spectrum () or substantially strengthen the confirmation of genes with limited evidence in the medical literature (). Routine diagnostics can provide valuable information on disease associations and support for genes without requiring tremendous research efforts. Thus, our results validate and delineate gene-disorder associations with the aim of motivating clinicians and scientists in diagnostic departments to provide additional evidence via publicly available databases or by publishing short case reports.
常规诊断偏向于有充分证据的基因和变异，但可能会错过那些罕见疾病，这些疾病的致病性只有很少的确认。然而，其中许多基因可以被认为是相关的，尽管它们的证据可能较少，因为它们缺乏 OMIM 条目，或者只包含来自一两个研究的少数公开可用的变异。在这里，我们介绍了 89 名个体，他们携带 77 个基因的变异，这些基因的临床意义只有少量的公开证据，但我们仍然认为这些证据足以在常规诊断中报告。对于 21 个基因，我们提供了病例报告，这些报告证实了 OMIM 关联的缺乏或临时性（），拓宽了表型谱（），或者大大加强了在医学文献中对证据有限的基因的确认（）。常规诊断可以提供有价值的疾病关联信息，并为没有大量研究工作的基因提供支持。因此，我们的结果验证和描绘了基因-疾病的关联，旨在激励诊断部门的临床医生和科学家通过公开可用的数据库或发表简短的病例报告提供额外的证据。
