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PKD1 – Autosomal Recessive Polycystic Kidney Disease

In two unrelated pedigrees, compound heterozygosity for hypomorphic and inactivating PKD1 alleles resulted in neonatal-onset polycystic kidney disease mirroring autosomal recessive polycystic kidney disease (PMID:20558538). Four patients (two sib-pairs) exhibited in utero massive renal cysts with no detectable PKHD1 variants, consistent with autosomal recessive inheritance of PKD1 under a hypomorphic mechanism. A key variant is c.4500G>C (p.Trp1500Cys).

These observations support a limited but clinically actionable association. PKD1 should be screened in patients presenting ARPKD-like features when PKHD1 testing is negative. Key take-home: compound heterozygous PKD1 alleles can phenocopy ARPKD and warrant inclusion in diagnostic panels.

References

  • Journal of the American Society of Nephrology • 2010 • Incompletely penetrant PKD1 alleles mimic the renal manifestations of ARPKD PMID:20558538

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

4 probands in 2 families ([PMID:20558538])

Genetic Evidence

Limited

Compound heterozygous hypomorphic PKD1 variants in trans recapitulate ARPKD phenotype in 4 patients ([PMID:20558538])

Functional Evidence

No Evidence

No functional studies specifically address PKD1 variant effects in ARPKD context