Case report: identification of one frameshift variant and two non-canonical splice variants of gene in prenatal arthrogryposis.

mutation is associated with congenital nemaline myopathies. Here, we report a family with recurrent prenatal arthrogryposis. Trio whole exome sequencing (WES) disclosed three novel (NM_001271208.2) variants including one paternal frameshift c.19049_19050delCA (p.Thr6350Argfs*14) and two double maternal variants in c. [24871G>T;24871-10C>G] (p. [Val8291Phe;?]). They are evaluated as "likely pathogenic (LP)", "variant of uncertain of significance (VUS)", and "VUS", respectively. After further prediction, the c.24871G>T, c.24871-10C>G, and c.[24871G>T;24871-10C>G] were respectively genetically engineered into the three plasmids. Compared with their wild-type counterparts, the three plasmids all produced truncated transcripts, and also a significant proportion of the full-length transcripts, which allowed us to reclassify c.24871G>T and c.24871-10C>G variants as LP. As far as we know, this is the first case carrying allele-specific function of partial loss. This result helped the couple make informed reproductive choices and opt for assisted reproduction for future pregnancies. This study also increased awareness to the phenotype of prenatal nemaline myopathy and expanded the variant spectrum of .