Weekly issue 2026-W40 ·
Beyond Sequencing: Integrating MLPA Reveals Hidden Structural PKD2 Variants and Enhances Mutation Detection in a Highly Selected ADPKD Greek Cohort
Plain language
Some people with ADPKD only need dialysis or a transplant late in life, which often points to the milder PKD2 form. In six Greek patients who started kidney replacement after age 70, standard gene reading found some causes, but one large missing piece of the PKD2 gene only showed up with an extra test called MLPA. If a genetic test found nothing, ask whether this kind of test for missing or duplicated gene pieces was included.
Clinical note
Small phenotype-enriched series: six consecutive ADPKD patients starting KRT after age 70, PKD2 Sanger sequencing plus MLPA. Pathogenic PKD2 variants in 2/6 (33%): recurrent p.Arg872Ter and a novel exon 1–9 deletion detectable only by MLPA; plus a novel VUS p.Leu273Gln. Argues that structural PKD2 variation is under-recognised in unresolved late-onset ADPKD and that NGS-negative cases warrant copy-number analysis. Very small cohort; yield not generalisable.
Question for your next visit
If my genetic test did not find a cause, did it look for missing or duplicated sections of PKD1 and PKD2, and is retesting worthwhile?