Table 2.

Notable cases where WES-based analysis conferred correct diagnoses or changed medical treatment strategies.

Initial clinical problem	Causal gene	Modified clinical interpretation (MIM number)	Significance of WES-based patient evaluation (treatment)	References
Developmental regression with Rett syndrome-like phenotype	ST3GAL5	Salt and pepper developmental regression syndrome (#609056)	Identified the molecular defect and established an accurate diagnosis	50,51
Hypotonia and motor delay followed by lower extremity weakness	DYNC1H1	Spinal muscular atrophy, lower extremity-predominant 1, AD (#158600)	Diagnosed a case with pleiotropic and evolving symptoms	52
Early onset hypotonia, sacral mass, congenital heart disease, and facial dysmorphism	ASAH1	Farber lipogranulomatosis (#228000)	Corrected a misdiagnosis	53
Ataxia followed by generalized dystonia	ANO3	Expanded spectrum of dystonia 24 (#615034)	Suggested a treatment strategy that resulted in gradual improvement within one year (deep brain stimulation)	54
Focal lower leg dystonia, dystonic gait	SLC2A1	GLUT1 deficiency syndrome 2 (#612126)	Identified disease-specific treatment that resulted in near-elimination of dystonia (ketogenic diet)	55
Leigh syndrome	SLC19A3	Thiamine metabolism dysfunction syndrome 2 (#606152)	Identified disease-specific treatment that resulted in clinical improvements in dystonia, spasticity, and cognitive function (supplements of thiamine and biotin)	56
Recurrent infections, telangiectatic skin mottling, and brain infarctions	TMEM173	STING-associated vasculopathy, infantile-onset (#615934)	Provided a rationale for a new treatment strategy that improved the skin lesions (tofacitinib treatment)	44
Severe global developmental delay, seizures, and acanthotic skin lesions	RAB11B	Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (#617807)	Identified a new disease gene leading to a neurodevelopmental syndrome	57