Incompletely Penetrant PKD1 Alleles Mimic the Renal Manifestations of ARPKD

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2010 Jun 19

PMID 20558538

Citations 79

Authors

Mihailo Vujic

Christina M Heyer

Elisabet Ars

Katharina Hopp

Arseni Markoff

Charlotte Orndal

Bengt Rudenhed

Samih H Nasr

Vicente E Torres

Roser Torra

Nadja Bogdanova

Peter C Harris

Affiliations

Soon will be listed here.

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutation in PKD1 or PKD2, is usually an adult-onset disorder but can rarely manifest as a neonatal disease within a family characterized by otherwise typical ADPKD. Coinheritance of a hypomorphic PKD1 allele in trans with an inactivating PKD1 allele is one mechanism that can cause early onset ADPKD. Here, we describe two pedigrees without a history of cystic kidney disease that each contain two patients with onset of massive PKD in utero. The presentations were typical of autosomal recessive PKD (ARPKD) but they were not linked to the known ARPKD gene, PKHD1. Mutation analysis of the ADPKD genes provided strong evidence that both families inherited, in trans, two incompletely penetrant PKD1 alleles. These patients illustrate that PKD1 mutations can manifest as a phenocopy of ARPKD with respect to renal involvement and highlight the perils of linkage-based diagnostics in ARPKD without positive PKHD1 mutation data. Furthermore, the phenotypic overlap between ARPKD and these patients resulting from incomplete penetrant PKD1 alleles support a common pathogenesis for these diseases.

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