There is abundant evidence published associating the DIS3L2 gene with Perlman syndrome, since the gene-disease relationship was first proposed by Astuti D, et al., 2012. Multiple case level studies (8 families) have been performed with Perlman syndrome patients that have variants in the DIS3L2 gene. The maximum points for genetic evidence has been reached (12 points). Abnormal expression of transcripts have been detected in cells from patients. Mutant DIS3L2 proteins lacking either exon 6 or exon 9 did not show substantial ribonuclease activity and results in aneuploidy and mitotic errors. DIS3L2 overexpression suppressed the growth of human cancer cell lines, and knockdown enhanced the growth of these cells. Phenotypes consistent with Perlman syndrome have been reported in three mouse models and one zebrafish model. All of these types of evidence are consistent with a definitive relationship between the DIS3L2 gene and Perlman 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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