YARS1 was first reported in relation to autosomal dominant Charcot-Marie-Tooth Disease in 2006 (Jordanova et al., PMID: 16429158). At least 8 unique variants have been reported in humans, including missense and indels. Evidence supporting this gene-disease relationship includes case level data, segregation data, and experimental data. Variants in this gene have been reported in at least 8 probands in 6 different publications (PMIDs: 24627108, 27027447, 16429158, 24354524, 26257172, 30373780). Variants in this gene have also segregated with disease in 34 additional family members across two different families. This gene-disease relationship is supported by animal models and functional studies. In drosophila models, expression of mutant YARS1 resulted in progressive motor impairment, electrophysiological deficits, and impaired protein translation (PMIDs: 19561293, 26138142). In cell culture, expression of mutant YARS1 was shown to result in transcriptional dysregulation through alterations of interactions between YARS1 and transcriptional regulators, leading to hyperactivation of E2F1 (PMID:31695036). In summary, YARS1 is DEFINITIVELY associated with autosomal dominant Charcot-Marie-Tooth Disease. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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