Genomics in Clinical Practice: Lessons from the Front Lines

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Science Translational Medicine  17 Jul 2013:
Vol. 5, Issue 194, pp. 194cm5
DOI: 10.1126/scitranslmed.3006468


  • 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.



  • 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
    1T cell immune deficiency4 pathogenic, 1 VUSNo
    2Multiple congenital anomalies, lactic acidosis, leukodystrophy and seizure disorder3 pathogenic, 11 VUSMaybe
    3Immune deficiency1 pathogenic, 1 VUSNo
    4Leukodystrophy3 pathogenic, 4 VUSMaybe
    5Intrauterine growth retardation, hair abnormalities, vomiting, chronic diarrhea, developmental delay, facial dysmorphism2 pathogenic, 5 VUSYes
    6Recurrent stroke, polymositis, chronic inflammation, recurrent unexplained fever5 pathogenic, 5 VUSNo
    7Infantile spasms, dystonia, sensorineural hearing loss, optic nerve abnormalities5 pathogenic, 10 VUSNo
    8Ataxia, seizures, regression1 pathogenic, 4 VUSNo
    9Malignant nerve sheath tumor, plexiform neurofibroma1 VUSNo
    10Dilated cardiomyopathy with recurrent hypoglycemic events2 VUSMaybe
    11Atypical hemolytic uremic syndrome1 VUSNo
    12Dystonia, chorea, mental retardation, retinal and neurotransmitter abnormalities2 pathogenic, 14 VUSMaybe
    13Recurrent rhabdomyolysis1 pathogenic, 6 VUSYes
    14Long QT syndrome, arrhythmia, neurogenic myopathy2 pathogenic, 5 VUSYes
    15Seizures with combined white and grey matter degeneration3 pathogenic, 1 VUSNo
    16Methyl malonic acidemia and spherocytosis1 pathogenicYes
    17Congenital myofibromatosis1 pathogenic, 5 VUSNo
    18Poor growth, vomiting, mental retardation, facial dysmorphism, seizure disorder2 pathogenic, 2 VUSYes
    19Connective tissue disorder, aortic root dilatation, short stature, developmental delay, hypermobilityanalysis in processN/A
    20Neurological condition (microcephaly, epilepsy, mental retardation, autism) and endocrine syndrome (primary ovarian failure)4 pathogenic, 1 VUSMaybe
    21Neurological condition (microcephaly, epilepsy, mental retardation, autism) and endocrine syndrome (primary ovarian failure)9 pathogenic, 2 VUSMaybe
    22Metabolic condition, liver and renal failure, bilateral cataracts, short stature3 pathogenic, 2 VUSMaybe
    23Neurological condition, neurodegenerationanalysis in processN/A
    Adult case #
    24Hypertension of unclear etiology (Executive Medicine Program)2 pathogenic, 3 VUSYes
    25Colon cancer, secondary finding of Marfan syndrome1 pathogenic, 8 VUSYes 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).

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