Comparative transcriptome analysis of skeletal muscle in ADSSL1 myopathy.

ADSSL1 myopathy was recently identified as the cause of muscular disorders in Korean patients with distal myopathy. We generated transcriptome profiles of muscles from control subjects and patients with ADSSL1 myopathy. In the present study, RNA sequencing was conducted with seven vastus lateralis muscle samples from four patients with ADSSL1 myopathy and three control subjects. The hierarchical clustering result revealed a separation between myopathy and control groups. A total of 1,260 transcripts were significantly differentially expressed (|fold change| ≥ 2, p < 0.05), with 740 upregulated transcripts and 520 downregulated transcripts in myopathy group. Eighteen transcripts that mapped to purine metabolism pathway were significantly differentially expressed between the two groups, with ten downregulated transcripts and eight upregulated transcripts in myopathy group. In particular, three genes involved in purine nucleotide cycle (ADSSL1, ADSL, and AMPD1) were significantly downregulated in myopathy group. Ten transcripts in glycolysis/gluconeogenesis pathway were also significantly differentially expressed. This is the first study on the altered expression of transcripts in muscle tissues from patients with ADSSL1 myopathy. Our results provide new insights into the pathogenesis of ADSSL1 myopathy.