Figures
Fig. 1 The long and winding road. Shown is the linear flow for a patient undergoing WGS in our genomic medicine clinic. Patients can enter the program at several points. A typical patient is referred by their clinician or is already in our hospital system. The first steps are collecting data from their records, a visit (outpatient or inpatient), genetic counseling, and discussion and determination of what data they would like returned to them. Once the patient has consented to clinical care, their genome is sequenced. Subsequent analysis focuses on the primary clinical reason the patient was admitted. Any secondary findings that the patient has requested are returned later. We then invite patients to come back annually for clinical follow-up. Ongoing care depends on the clinical presentation, severity of symptoms, and the outcome of our assessment. We also allow patients to enter the system with their own genome sequence in hand as long as the sequence was generated in a CLIA/CAP-accredited laboratory.
CREDIT: H. McDONALD/SCIENCE TRANSLATIONAL MEDICINE
Tables
- Table 1
Results of WGS at the MCW Genomics Medicine Clinic for 23 Pediatric (CHW) and 2 Adult (FH) Cases.
Pediatric case # Clinical indication Variants Diagnosis 1 T cell immune deficiency 4 pathogenic, 1 VUS No 2 Multiple congenital anomalies, lactic acidosis, leukodystrophy and seizure disorder 3 pathogenic, 11 VUS Maybe 3 Immune deficiency 1 pathogenic, 1 VUS No 4 Leukodystrophy 3 pathogenic, 4 VUS Maybe 5 Intrauterine growth retardation, hair abnormalities, vomiting, chronic diarrhea, developmental delay, facial dysmorphism 2 pathogenic, 5 VUS Yes 6 Recurrent stroke, polymositis, chronic inflammation, recurrent unexplained fever 5 pathogenic, 5 VUS No 7 Infantile spasms, dystonia, sensorineural hearing loss, optic nerve abnormalities 5 pathogenic, 10 VUS No 8 Ataxia, seizures, regression 1 pathogenic, 4 VUS No 9 Malignant nerve sheath tumor, plexiform neurofibroma 1 VUS No 10 Dilated cardiomyopathy with recurrent hypoglycemic events 2 VUS Maybe 11 Atypical hemolytic uremic syndrome 1 VUS No 12 Dystonia, chorea, mental retardation, retinal and neurotransmitter abnormalities 2 pathogenic, 14 VUS Maybe 13 Recurrent rhabdomyolysis 1 pathogenic, 6 VUS Yes 14 Long QT syndrome, arrhythmia, neurogenic myopathy 2 pathogenic, 5 VUS Yes 15 Seizures with combined white and grey matter degeneration 3 pathogenic, 1 VUS No 16 Methyl malonic acidemia and spherocytosis 1 pathogenic Yes 17 Congenital myofibromatosis 1 pathogenic, 5 VUS No 18 Poor growth, vomiting, mental retardation, facial dysmorphism, seizure disorder 2 pathogenic, 2 VUS Yes 19 Connective tissue disorder, aortic root dilatation, short stature, developmental delay, hypermobility analysis in process N/A 20 Neurological condition (microcephaly, epilepsy, mental retardation, autism) and endocrine syndrome (primary ovarian failure) 4 pathogenic, 1 VUS Maybe 21 Neurological condition (microcephaly, epilepsy, mental retardation, autism) and endocrine syndrome (primary ovarian failure) 9 pathogenic, 2 VUS Maybe 22 Metabolic condition, liver and renal failure, bilateral cataracts, short stature 3 pathogenic, 2 VUS Maybe 23 Neurological condition, neurodegeneration analysis in process N/A Adult case # 24 Hypertension of unclear etiology (Executive Medicine Program) 2 pathogenic, 3 VUS Yes 25 Colon cancer, secondary finding of Marfan syndrome 1 pathogenic, 8 VUS Yes for Marfan syndrome; Maybe for cancer The first column lists the order in which patient samples were sent to Illumina for whole-genome sequencing (WGS). Nic Volker is not listed because his diagnosis was made using whole-exome sequencing. Clinical indication denotes the broad category of disease the patient initially presented with. The ACMG guidelines were used to classify variants as either pathogenic or variant of uncertain significance (VUS). N/A, not analyzed. Children’s Hospital of Wisconsin (CHW), Froedtert Hospital (FH), Medical College of Wisconsin (MCW).
