Skip to main content

Conference Program

Subpage Hero


Think Rare: Solving the Undiagnosed Cases Beyond Exome or Genome Sequencing

13 Mar 2024
Venue: MTCC
Meeting Room: 701
Laboratory Genetics & Genomics
  • Accredited:
    • Accredited
  • Primary Categories:
    • Clinical Genetics
  • Secondary Categories:
    • Clinical Genetics
  • Level of Learner:
    • Intermediate
Over the past decade, advances in genomic testing, particularly exome sequencing (ES) or genome sequencing (GS), have significantly improved the diagnostic yield. Nonetheless, many patients are still left without a molecular diagnosis. Given the challenges and limitations of current next-generation sequencing-based technology, a “negative” ES or GS should not be considered the end of the quest for a diagnosis. Despite the wide application of this technology, we should not overlook the value of seemingly “outdated” tests, such as a karyotype, SNP array, FISH, as well as thorough history taking and physical examination. Moreover, complex structural variants in the genome, such as inversions or translocations, may be missed by conventional next-generation sequencing. The detection of somatic mosaicism relies on sampling the appropriate tissue. The absence of genetic sequencing variants does not preclude epigenetic abnormalities. Classification of non-coding variants requires collaborative functional studies.  Unexpected or unusual modes of inheritance should also be considered during genomic data analysis. It is important that trainees and practicing geneticists remember that there is a larger armamentarium of testing than simply ES/GS. The judicious use of a broad spectrum of old and new genetic technologies will increase diagnostic yield.

An expert panel of five speakers will describe clinical vignettes with negative ES or GS, illustrating how they solved undiagnosed cases with unusual structural variants, copy number variants, mosaicism, imprinting disorder/abnormal methylation, or non-coding variants. We hope this session will serve as a guide for clinicians and researchers to proactively explore to achieve a precise molecular diagnosis in modern genomic medicine practice.

Learning Objectives

  1. Identify advantages and limitations of next generation sequencing and various diagnostic genetic testing
  2. Appreciate the challenges in interpreting non-coding variants and structural variants
  3. Recognize the importance of clinical skill of deep phenotyping in modern genetic practice
  4. Initiate communication between the clinical team and diagnostic lab to increase diagnostic yield