for people ages up to 18 years (full criteria)
study started
estimated completion
Principal Investigator
by Pui-Yan Kwok, MD/PhD (ucsf)Barbara Koenig, PhD (ucsf)Mary Norton, MD (ucsf)
Headshot of Barbara Koenig
Barbara Koenig



The investigator aims to examine the clinical utility of WES, including assessment of a variety of clinical outcomes in undiagnosed pediatric cases.

Official Title

Genomic Sequencing to Aid Diagnosis in Pediatric and Prenatal Practice: Examining Clinical Utility, Ethical Implications, Payer Coverage, and Data Integration in a Diverse Population.


Next-generation sequencing (NGS) is changing the paradigm of clinical genetic testing. Unlike highly focused single-gene tests, NGS allows one to examine gene panels, the exome, and the whole genome. With the broad array of molecular tests now available, ordering physicians face the conundrum of selecting the best diagnostic tool for patients with suspected genetic conditions. Single-gene testing is often most appropriate for conditions with distinctive clinical features and minimal locus heterogeneity. NGS-based gene panel testing, which can be complemented with chromosomal microarray analysis (CMA) and other ancillary methods, provides a comprehensive and feasible approach for well documented but genetically heterogeneous disorders. Whole exome sequencing (WES) and whole genome sequencing (WGS) have the advantage of enabling parallel interrogation of most of the genes in the human genome. To some, WES is preferable to previously used methods due to higher diagnostic yield, shorter time to diagnosis, and improved cost-efficiency. The ability to survey the exome opens up both new opportunities and new challenges. For example, all coding regions of known genes must be analyzed when applying WES to undiagnosed cases with unclear inheritance patterns. Current limitations on variant interpretation capabilities and clinical validity raise questions about the clinical utility of WES as either a stand-alone or a first-choice diagnostic test. Additional challenges include pre- and post-test counseling with appropriate and robust informed consent, bioinformatics analysis setup and validation, variant interpretation and classification, the need for policies and protocols concerning the discovery and reporting of secondary findings unrelated to the presenting indication, a requirement for validation of WES results, assurance of conformation to quality control standards, data storage and accessibility, and reimbursement issues. Introducing WES into pediatric clinical care of underrepresented populations raises additional issues and considerations of payment coverage, access, and standards of care. Beyond the sheer complexity of the test and its results, clinicians and health systems must address numerous considerations, including: private and public insurance coverage; language and culture differences and their implications for genetic counseling and clinician-patient relationships; ability to access follow-up testing and clinical care; and ability to access appropriate treatment and services. These issues and others will affect not only patients' decision-making regarding WES, but also their post-test needs for patient follow up. The importance of systematically assessing the clinical utility of NGS is critical for determining in which clinical and health care contexts WES will be useful and for commencing research on these considerations.


Encephalopathy Birth Defect Intellectual Disability Multiple Congenital Anomaly Metabolic Disease Epilepsy Neuro-Degenerative Disease Cerebral Palsy Developmental Delay Developmental Defect Exome Sequencing Clinical Utility Pediatric Underrepresented Underserved Brain Diseases Neurodegenerative Diseases Congenital Abnormalities Abnormalities, Multiple Metabolic Diseases Whole Exome Sequencing


You can join if…

Open to people ages up to 18 years

  1. Presenting clinical features suggestive of a genetic etiology, including intellectual disability, seizures, multiple congenital anomalies, metabolic conditions, and neurodegenerative conditions or idiopathic cerebral palsy.
  2. A minimum of one biological parent is available and willing to provide a specimen for WES, with a preference for two available parents. At least one parent consenting to WES of the child.
  3. Pediatric patients must have had at least one prior genetics appointment or evaluation
  4. Pediatric patients may have had a single nucleotide polymorphism (SNP) array or oligonucleotide array that did not provide a diagnosis.

You CAN'T join if...

  1. Prior WES performed for a clinical or research indication
  2. Lack of phenotypic indication of a likely underlying genetic etiology
  3. Both biological parents are unavailable.


  • UCSF Fresno
    Fresno California 93701 United States
  • UCSF Benioff Children's Hospital Oakland
    Oakland California 94609 United States
  • Zuckerberg San Francisco General Hospital
    San Francisco California 94110 United States
  • Benioff Children's Hospital Mission Bay
    San Francisco California 94158 United States

Lead Scientists at University of California Health

  • Pui-Yan Kwok, MD/PhD (ucsf)
    Professor, Cardiovascular Research Inst, School of Medicine. Authored (or co-authored) 283 research publications
  • Barbara Koenig, PhD (ucsf)
    Professor, Institute for Health & Aging, School of Nursing. Authored (or co-authored) 158 research publications
  • Mary Norton, MD (ucsf)
    Professor, Ob/Gyn, Reproductive Sciences, School of Medicine. Authored (or co-authored) 234 research publications


in progress, not accepting new patients
Start Date
Completion Date
University of California, San Francisco
Study Type
Expecting 800 study participants
Last Updated