Molecular characteristics

Currently, molecular diagnostics in LDS patients most typically involves gene panel sequencing or exome sequencing. The majority of the LDS5-causing TGFB3 genetic defects consist of genetic variants substituting a single amino acid (missense mutations; 60%), whereas 20% disturb the protein’s reading frame (frameshift mutations), 13% introduce a premature stopcodon (nonsense mutations), and 7% affect a splice site. Because of the frequent occurrence of truncating mutations, it is hypothesized that TGFB3 mutations lead to loss of function of the encoded protein.