Truncating variants in the penultimate exon of TGFBR1 escaping nonsense-mediated mRNA decay cause Loeys-Dietz syndrome.

ABSTRACT: Pathogenic variants in TGFBR1 are a common cause of Loeys-Dietz syndrome (LDS) characterized by life-threatening aortic and arterial disease. Generally, these are missense changes in highly conserved amino acids in the serine-threonine kinase domain. Conversely, nonsense, frameshift, or specific missense changes in the ligand-binding extracellular domain cause multiple self-healing squamous epithelioma (MSSE) lacking the cardiovascular phenotype. Here, we report on two novel variants in the penultimate exon 8 of TGFBR1 were identified in 3 patients from two unrelated LDS families: both were predicted to cause frameshift and premature stop codons (Gln448Profs*15 and Cys446Asnfs*4) resulting in truncated TGFBR1 proteins lacking the last 43 and 56 amino acid residues, respectively. These were

SUBMITTER: Fortugno P 

PROVIDER: S-EPMC10172188 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature