Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders

摘要: Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at 1000 loci. Traditional methods yield molecular diagnoses in less one-half with NDD. Whole-genome sequencing (WGS) whole-exome (WES) can enable diagnosis NDD, but their clinical cost-effectiveness unknown. One hundred families 119 affected by NDD received diagnostic WGS and/or WES parent-child trios, wherein the approach was guided acuity illness. Forty-five percent diagnoses. An accelerated modality, rapid WGS, yielded 73% acutely ill (11 15). Forty nonacute followed ambulatory care clinics (34 85), diagnoses: 33 1 staged then WGS. The cost prior negative tests patients $19,100 per family, suggesting be cost-effective up $7640 family. A change or impression pathophysiology reported 49% newly diagnosed families. If had been performed symptom onset, genomic may have made 77 months earlier occurred this study. It is suggested that initial evaluation should include trio WES, extension modalities high-acuity patients.