Figure 1. Reverse phenotyping.

Schematic of the phenotype-first (green) versus the genotype-first (also referred to as reverse phenotyping, blue) approaches for identification of causal gene mutations. The phenotype-first approach relies on identification of patients and families, collection of clinical data, accurate research diagnosis, and, finally, collection of genotype data steps. In the genotype-first approach, the process is reversed and starts with the analysis of genomic data and selection of candidate variants followed by comprehensive clinical phenotyping of patients and families to make accurate genotype-phenotype correlations.