The majority of the LDS3-causing SMAD3 genetic defects result in substitution of a single amino acid (61%), disturbance of the protein’s reading frame (23%), introduction of a premature stopcodon (7%) and perturbation of a splice site (6%). SMAD3 genetic defects are predicted to lead to loss of function of the encoded protein.
Currently, molecular diagnostics in LDS patients most typically involves gene panel sequencing or exome sequencing.