Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Multidisciplinary Workshop #1 - Family History, Genetic Testing, and Understanding ACMG Classification

Video Transcription

Video Summary

The session is a multidisciplinary workshop on practical genetics for kidney disease, focused on improving family history taking, interpreting genetic test reports, and managing negative or uncertain results. Speakers stress avoiding the phrase “no family history,” because it may mean “unknown,” and because variable penetrance, limited healthcare access, and nonspecific questioning can hide inherited disease. Clinicians are encouraged to ask targeted questions (dialysis, transplant, early/sudden death, age at diagnosis), reassess family history over time, and document it with pedigrees to recognize inheritance patterns and consanguinity.<br /><br />Participants complete an interactive exercise: one person plays a 37-year-old man with hypertension and cystic kidney disease; others interview and draw a pedigree. The case includes atypical imaging features and neurodevelopmental findings, prompting genetic testing.<br /><br />Faculty review how genetic reports are structured and how to interpret variant types and classifications (benign, VUS, likely pathogenic, pathogenic). They explain that some genes (e.g., UMOD) have specific disease mechanisms (toxic gain-of-function), so loss-of-function variants may not be pathogenic. Alicia Byrne provides a brief overview of ACMG/AMP variant classification evidence categories and upcoming guideline changes, emphasizing that VUSs should not guide management but can be clarified through phenotype sharing, segregation testing, expert consultation, and reanalysis—especially important for underrepresented ancestries.<br /><br />The case ultimately resolves via chromosomal microarray showing an HNF1B deletion, underscoring test limitations and that “negative” doesn’t exclude a genetic cause.

Asset Subtitle

Alicia Brigitte Byrne, Matthew Lanktree, Hila Milo Rasouly

Meta Tag

Module GENE

Speaker FACULTY FACULTY

Keywords

kidney disease genetics

family history taking

pedigree analysis

genetic test report interpretation

ACMG/AMP variant classification

variant of uncertain significance (VUS) management

UMOD toxic gain-of-function

HNF1B deletion

chromosomal microarray