Genomics in Autism Routine Clinical Care and Research

Presented by:
David H. Ledbetter, PhD, FACMG
Chief Clinical & Research Officer
Unified Patient Network
Seven Bridges Genomics

Faculty Disclosure:

“Dr Ledbetter has disclosed that he is a consultant for Natera, Inc. & MyOme, Inc. as well as a stock shareholder for X-Therma, Inc. and a full-time employee/executive of Unified Patient Network, Inc. No one else in a position to control content has any financial relationships to disclose.”

Conflict of interest information for the CME Advisory Committee members can be found on the following website: https://cme.ufl.edu/disclosure/. All relevant financial relationships have been mitigated.

Release Date: 4/25/22
Expiration Date:  4/24/25

Target Audience: All physicians

Learning Objectives:

As a result of participation in this activity, participants should be able to:

  1. Recognize that a significant percentage (30-40%) of individuals with autism and related neurodevelopmental disorders (NDD) have an underlying rare genetic disease that can be identified by routine clinical genetic testing (microarray, exome sequencing, genome sequencing).
  2. Describe the value of identifying a specific genetic cause of a child’s NDD, including ending the diagnostic odyssey, establishing accurate recurrence risk for parents, informing prognosis and often directly impacting medical and educational management plans.
  3. Differentiate between the genetic concepts of incomplete penetrance and clinical variability as it applies to dimensional (quantitative) traits such as cognitive ability (e.g., IQ) and social behavior (e.g., SRS).
  4. Recognize the role of both rare genomic variants with large effect size and common genomic variants with individually small effect sizes but cumulatively large effects, as well as the interplay of these two classes of genomic variants (largely additive).

 

Requirements for successful completion: Certificates are awarded upon successful completion (80% proficiency) of the post-test.

Accreditation: The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit: The University of Florida College of Medicine designates this enduring material for a maximum of __1_ AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Resource(s) for further study:

  1. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders, Genetics in Medicine, 2019 Nov; 21(11): 2413-2421. Doi: 10.1038/s41436-019-0554-6. Epub 2019 Jun 11. https://pubmed.ncbi.nlm.nih.gov/31182824/
  2. Clinical Genetic Testing in Autism Spectrum Disorder in a Large Community-Based Population Sample, JAMA Psychiatry, September 2020, Vol. 77, No. 9. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2765958
  3. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care – Preliminary Report, The New England Journal of Medicine, Nov. 11, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2035790
  4. Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK. Lancet Neurol 2022; 21:234-45. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00462-2/fulltext
  5. Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence. Lancet Neurol 2013; 12:406-14. https://pubmed.ncbi.nlm.nih.gov/23518333/
  6. Single Nucleotide Variants (SNV) Span DBD. Lancet Neurol 2013.
  7. Community Health Initiative. Genetics in Medicine. Carey et al 2016.
  8. Regeneron and Geisinger first 50K exomes. The DiscovEHR Research Cohort (Science, Dec. 23, 2016).
  9. MyCode Genomics Screening Summary, Buchanan et al, Genetics in Medicine, June 2020.
  10. Nordestgaard et al (2013). Eur Heart J 34:3478-3490.
  11. Childers et al (2017). J Clin Oncol 35:3800-3806.
  12. Identification of Neuropsychiatric Copy Number Variants in a Health Care System Population, JAMA Psychiatry, July 22, 2020. PMID: 32697297. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2768030
  13. Martin, Wain et al, JAMA Psych 2020.
  14. Psychopathology in adults with copy number variants, Psychological Medicine, 2022. https://www.cambridge.org/core/journals/psychological-medicine/article/psychopathology-in-adults-with-copy-number-variants/70764398AA8DB9443F6993DAE9F81055
  15. Medical manifestations and health care utilization among adult MyCode participants with neurodevelopmental psychiatric copy number variants, Genetics in Medicine, 2022. https://www.sciencedirect.com/science/article/pii/S1098360021053880?v=s5

If you have any questions please feel free to contact Nancy Boyd at (352) 594-4298 or at nancy.boyd@ufl.edu