Marais, AnettBertoli-Avella, Aida M.Beetz, ChristianAltunoğlu, UmutAlhashem, AmalMohamed, SararAlghamdi, AbdulazizWillems, PatrickTsoutsou, EiriniFryssira, HelenaPons, RoserAlmarzooq, ReemYüksel Karatoprak, ElifAyaz, AkifÜnverengil, GökçenCalvo, MariaYüksel, ZaferBauer, Peter2022-07-042022-07-042022Marais, A., Bertoli-Avella, A. M., Beetz, C., Altunoğlu, U., Alhashem, A., Mohamed, S. ... Bauer, P. (2022). Further clinical and genetic evidence of ASC-1 complex dysfunction in congenital neuromuscular disease. European Journal of Medical Genetics, 65(8). http://doi.org/10.1016/j.ejmg.2022.1045371769-72121878-0849http://doi.org/10.1016/j.ejmg.2022.104537https://hdl.handle.net/20.500.12511/9556Transcriptional 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.eninfo:eu-repo/semantics/embargoedAccessASC-1ASCC1MyopathySpinal Muscular AtrophyTranscriptional CoregulatorTRIP4Article65810.1016/j.ejmg.2022.104537N/A0008362879000032-s2.0-8513233576935690317Q2