SMABF2 is caused by biallelic genomic variants, i.e. present in both copies of the ASCC1 (*614215) gene, located on chromosome 10. This gene produces a protein that participates in the formation of a protein complex, called ASC-1, together with 3 other components: TRIP4 (or ASC1; *604501), ASCC2 (*614216), and ASCC3 (*614217) involved in several biological processes, such as DNA damage repair and gene expression regulation. Although not well established yet, the gene plays a pivotal role in muscular cells, regulating the muscular tissue development.
All the genomic variants described in the patients are predicted to lead to the complete absence of the proteic product of the gene.
Recently, two gene variants found in compound heterozygosity in a patient with a distinct clinical condition characterized by neonatal hypotonia, delayed early motor and language development, but no dysphagia, no dysphonia, no respiratory dysfunction and no congenital fractures, except the ulnar epiphysiolysis observed in neonatal period. This milder phenotype has been supposed was due to the presence of an altered albeit present protein.
ASCC1