QARS was reported in relation to diffuse cerebral and cerebellar atrophy-intractable seizures – progressive microcephaly syndrome in 2014 (PMID: 24656866). Evidence supporting this gene-disease relationship is case-level data and functional characterization. Variants in this gene have been reported in at least 8 individuals, including 2 sets of affected siblings (PMID: 27717089, 31618474, 25471517, 25432320, 24656866). This is insufficient to reach the maximum amount of case level data. However, several additional pathogenic LoF variants are reported in ClinVar. Variants in this gene are known to disrupt the protein interactions with other disease genes, RARS (PMID: 24656866). Additionally a knock-out zebrafish model was generated with recapitulated the human phenotype (PMID: 24656866). The mechanism for disease is loss of function. In summary, QARS is definitively associated with diffuse cerebral and cerebellar atrophy-intractable seizures – progressive microcephaly syndrome.
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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