Figure 3.

From phenotype to genotype, and back. (A) Genetic testing can be used to confirm the clinical suspect of a genetic disease, looking for mutations in disease-causing genes (from phenotype to genotype). Genetic testing can be performed either with traditional Sanger sequencing (if only one gene can cause the phenotype or if the clinical suspect is extremely high) or with NGS (if more than one gene is known to cause the disease). (B) Extended genotyping can result in unexpected genetic findings (i.e., mutations in genes not classically reported in association with the clinical phenotype of the patient). Reverse phenotyping represents a strategy to verify the hypothesis of a specific genetic diagnosis (from genotype to phenotype). By looking for subtle, previously overlooked clinical signs or symptoms related to the genetic diagnosis, reverse phenotyping can reclassify the diagnosis and initiate personalized clinical management.