Clinical Utility of Pediatric Whole Exome Sequencing

NCT03525431 | Completed Results FDA Device

• 2 other identifiers: 1U01HG009599-01U01HG009599
• Study Type: interventional
• Target: 529
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Encephalopathy; Birth Defect; Intellectual Disability; Multiple Congenital Anomaly; Metabolic Disease; Epilepsy; Neuro-Degenerative Disease; Cerebral Palsy; Developmental Delay; Developmental Defect

Keywords

Exome; Sequencing; Clinical Utility; Pediatric; Underrepresented; Underserved

Outcome Measures

Primary Outcomes (1)

• Number of Pediatric Patients With a Positive Exome Sequencing Result

  Number of pediatric patients with a diagnostic result among all patients where exome was performed. A positive exome sequencing result means the identification of a pathogenic or likely pathogenic gene variant to explain the child's condition. The definition of pediatric was expanded to include participants over the age of 18 if they were being followed by UCSF pediatrics department if they were patients at the pediatrics department before they were 18 years old.

  At the completion of data collection (follow-up visit at 6-12 months after return of results)

Study Arms (1)

Whole Exome Sequencing

EXPERIMENTAL

Following consent and collection of standardized phenotypic data, probands and biological parents will undergo WES with variant analysis conducted utilizing primary gene lists based on referring clinical indication. After results provision and follow up 6-12 months later, clinical utility will be assessed in those with a positive result (pathogenic or likely pathogenic variant) and those with negative results (no variant returned or a VUS) using specific outcomes at each site to examine effectiveness for both the child and family.

Diagnostic Test: Whole Exome Sequencing

Interventions

Whole Exome Sequencing DIAGNOSTIC_TEST

Whole Exome Sequencing is a form of Next Generation Sequencing allowing investigators to assess the coding regions of many thousands of genes to find variants implicated in disease.

Also known as: Next Generation Sequencing

Whole Exome Sequencing

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Presenting clinical features suggestive of a genetic etiology, including intellectual disability, seizures, multiple congenital anomalies, metabolic conditions, and neurodegenerative conditions or idiopathic cerebral palsy.
• 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.
• \. Pediatric patients must have had at least one prior genetics appointment or evaluation 5. Pediatric patients may have had a single nucleotide polymorphism (SNP) array or oligonucleotide array that did not provide a diagnosis.
• Even though this study is for pediatric patients, maximum age limit was increased to 25, if patients fulfilling the above criteria were being followed by Pediatrics Department since they were younger than 18.

You may not qualify if:

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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Human Genome Research Institute (NHGRI): collaborator

Study Sites (4)

UCSF Fresno

Fresno, California, 93701, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Benioff Children's Hospital Mission Bay

San Francisco, California, 94158, United States

Location

Related Publications (3)

• Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013 Oct 17;369(16):1502-11. doi: 10.1056/NEJMoa1306555. Epub 2013 Oct 2.

  PMID: 24088041 BACKGROUND

• Slavotinek A. Clinical care models in the era of next-generation sequencing. Mol Genet Genomic Med. 2016 May 12;4(3):239-42. doi: 10.1002/mgg3.225. eCollection 2016 May. No abstract available.

  PMID: 27247951 BACKGROUND

• Rego S, Hoban H, Outram S, Zamora AN, Chen F, Sahin-Hodoglugil N, Anguiano B, Norstad M, Yip T, Lianoglou B, Sparks TN, Norton ME, Koenig BA, Slavotinek AM, Ackerman SL. Perspectives and preferences regarding genomic secondary findings in underrepresented prenatal and pediatric populations: A mixed-methods approach. Genet Med. 2022 Jun;24(6):1206-1216. doi: 10.1016/j.gim.2022.02.004. Epub 2022 Apr 8.

  PMID: 35396980 DERIVED

MeSH Terms

Conditions

Brain Diseases; Congenital Abnormalities; Intellectual Disability; Abnormalities, Multiple; Metabolic Diseases; Epilepsy; Cerebral Palsy; Learning Disabilities

Interventions

Exome

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Nutritional and Metabolic Diseases; Brain Damage, Chronic; Communication Disorders

Intervention Hierarchy (Ancestors)

Genome; Genetic Structures; Genetic Phenomena

Results Point of Contact

• Title: Mary Norton
• Organization: University of California, San Francisco

mary.norton@ucsf.edu

(415) 476 4080

Study Officials

• Pui-Yan Kwok, MD/PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Barbara Koenig, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Mary Norton, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2018
• First Posted: May 15, 2018
• Study Start: August 1, 2017
• Primary Completion: May 13, 2022
• Study Completion: May 13, 2022
• Last Updated: July 18, 2023
• Results First Posted: July 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)