Spinal muscular atrophy with congenital bone fractures 2 caused by a rare loss‐of‐function ASCC1 gene mutation in two Bulgarian Roma patients

ASCC1 structures and bioinformatics reveal a novel helix-clasp-helix RNA-binding motif linked to a two-histidine phosphodiesterase

“…The significance of ASCC1 is found in the diseases associated with ASCC1 and/or ASC-1. ASCC1 and TRIP4 mutations are associated with a severe form of spinal muscular atrophy (SMA) with congenital Bone Fractures 2 (SMABF2) ( 6 , 7 , 8 , 9 , 10 , 11 , 13 , 79 , 80 , 81 , 82 ). Via the ASC-1 complex, SMA is linked to the fatal neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS).…”

“…Besides acting in alkylation damage, null/truncations mutations in ASCC1 are implicated in diseases such as Barrett’s esophagus and esophageal adenocarcinoma, spinal muscular atrophy with congenital bone fractures 2 (SMABF2), and rheumatoid arthritis ( Table S1 ) ( 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ). Almost all the known pathogenic ASCC1 variants are predicted to entail either premature truncation or complete absence of the ASCC1 protein suggesting the full-length protein is necessary for its function(s).…”