A Missense Mutation rs781536408 (c.2395G>A) of Affects Splicing and Causes Skipping of Exon18 .

variants can impact disease onset or progression. In our previous study, we identified abnormal splicing that happened near rs781536408 in the gene. The purpose of this research was to examine the effect of the mutation on alternative splicing and . Whole exome sequencing was performed to identify the mutations followed by bidirectional Sanger sequencing. Then the minigene analysis was carried out based on HeLa and HEK293T cell lines. The results showed that rs781536408 (c.2395G>A, p.G799R) was homozygous in the patient, but heterozygous in parents. PCR amplification confirmed the abnormal splicing in the somatic cells of the patients, but not in the parents. Sanger sequencing results showed that there was a skipping of exon18 near the mutation. For minigene analysis, there was no difference between the wild-type and the mutant type in the two minigene construction strategies, indicating that mutation c.2395G>A had no effect on splicing . Combining the results of , we speculated that the effect of the mutation on splicing was not absolute, but rather in degree.