Further clinical and genetic evidence of ASC-1 complex dysfunction in congenital neuromuscular disease

Marais A., Bertoli-Avella A. M., Beetz C., Altunoglu U., Alhashem A., Mohamed S., ...More

European Journal of Medical Genetics, vol.65, no.8, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 65 Issue: 8
  • Publication Date: 2022
  • Doi Number: 10.1016/j.ejmg.2022.104537
  • Journal Name: European Journal of Medical Genetics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, MEDLINE
  • Keywords: ASC-1, ASCC1, Myopathy, Spinal muscular atrophy, Transcriptional coregulator, TRIP4, MUTATIONS, DATABASE
  • Istanbul University Affiliated: Yes


© 2022 Elsevier Masson SASTranscriptional coregulators modulate the efficiency of transcription factors. Bi-allelic variants in TRIP4 and ASCC1, two genes that encode members of the tetrameric coregulator ASC-1, have recently been associated with congenital bone fractures, hypotonia, and muscular dystrophy in a total of 22 unrelated families. Upon exome sequencing and data repository mining, we identified six new patients with pathogenic homozygous variants in either TRIP4 (n = 4, two novel variants) or ASCC1 (n = 2, one novel variant). The associated clinical findings confirm and extend previous descriptions. Considering all patients reported to date, we provide supporting evidence suggesting that ASCC1-related disease has a more severe phenotype compared to TRIP4-related disorder regarding higher incidence of perinatal bone fractures and shorter survival.