To date, 20 different disease-causing genetic variants have been described. These variants result in either a substitution of a single amino acid or a deletion of multiple amino acids. All disease causing genetic variants are localized in the beginning of the gene implicating that the initial molecular testing could be focused on this part. Three mutational hotspots have been identified (amino acids 20-35, 94-117 and 180). Interestingly, with a whole gene deletion (1p36.3 deletion syndrome) a patient does not present with SGS phenotype, suggesting that a reduction of 50% of gene function is not the disease causing mechanism of action.
SKI