Figure 1
From: Genomic diagnostics within a medically underserved population: efficacy and implications
Molecular diagnostic algorithm (a) The standard diagnostic algorithm for each proband included population-specific allele detection, high-density chromosomal microarray (CMA), family whole-exome sequencing (WES), and posttest follow-up to refine phenotype, recruit additional relatives, and confirm segregation. (b) The pretest probability of Mendelian disease was high for 79 probands, 7 of whom had a pathogenic molecular karyotype by CMA. Seventy-two probands proceeded to WES, which allowed us to identify a definitive molecular diagnosis (n = 32; 44%) or find compelling evidence for a novel genetic mechanism (n = 5; 7%). In 5 (7%) additional subjects, “negative” WES reduced the likelihood of monogenic disease. Thirty cases remain “open” for iterative reanalysis. HPO, Human Phenotype Ontology.
