Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Nephrogenetic Clinical Cases

Video Transcription

Video Summary

A nephrologist from an academic center in Brest, France presents an interactive workshop on “clinical cases of nephrogenetics,” emphasizing that rare genetic kidney diseases occur everywhere, not just major referral centers.  

<strong>Case 1:</strong> A 49-year-old woman with advanced CKD (eGFR 19) and small atrophic kidneys with few cysts is evaluated for living-related transplant; both adult sons have normal ultrasounds. Rather than relying on imaging alone, the speaker argues for genetic testing in the recipient first, plus gathering extended family data. Exome sequencing identifies a “likely pathogenic” PKD1 variant, but the phenotype is inconsistent with ADPKD (no enlarged, massively cystic kidneys). The lab’s classification was biased by limited clinical information. Reanalysis using a pipeline able to detect difficult regions finds a pathogenic <strong>MUC1</strong> variant (ADTKD), a known diagnostic “blind spot.” This enables cascade testing and informed donor selection.

<strong>Case 2:</strong> A 24-year-old man presents late with ESRD, nephrotic-range proteinuria, anemia, and family history suggesting inherited disease. Detailed family/phenotype review reveals cryptorchidism/orchidopexy in affected males and a previously reported <strong>WT1</strong> VUS in the grandfather. Segregation across generations plus a specific syndromic feature supports upgrading the variant to likely pathogenic, highlighting how clinicians can help resolve VUS findings.

<strong>Case 3:</strong> A 28-year-old woman planning pregnancy seeks risk assessment due to family “IgA nephropathy”/“hypertensive nephropathy.” The speaker critiques vague labels and promotes “CKD/KF of unexplained cause (CKDX/KFX)” frameworks. Exome finds a <strong>JAG1</strong> variant consistent with Alagille syndrome, explaining renal disease and subtle cardiac history, guiding reproductive counseling, extra-renal screening, and donor evaluation.

Q&A covers preimplantation genetic testing, transplant cancer risk in WT1 disease, and the need for genetics education and counseling resources. The overarching message: interpret genetics through clinical context, investigate VUS results, and avoid imprecise diagnoses.

Asset Subtitle

Arlene B. Chapman, Emilie Cornec-Le Gall

Meta Tag

Module GENE

Speaker CO-CHAIRS CO-CHAIRS

Keywords

nephrogenetics

rare genetic kidney disease

exome sequencing

ADTKD

MUC1

PKD1 variant reclassification

WT1 variant of uncertain significance

Alagille syndrome

JAG1 mutation

cascade testing and living kidney donor selection