Incompletely Penetrant PKD1 Alleles Mimic the Renal Manifestations of ARPKD
Por:
Vujic, M, Heyer, CM, Ars, E, Hopp, K, Markoff, A, Orndal, C, Rudenhed, B, Nasr, SH, Torres, VE, Torra, R, Bogdanova, N, Harris, PC
Publicada:
1 jul 2010
Resumen:
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.
Filiaciones:
Vujic, M:
Sahlgrens Univ Hosp, Dept Clin Genet, Gothenburg, Sweden
Heyer, CM:
Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA
Ars, E:
Fundacio Puigvert, Mol Biol Lab, Barcelona, Spain
Hopp, K:
Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
Markoff, A:
Univ Munster, Ctr Mol Biol Inflammat, D-48149 Munster, Germany
Orndal, C:
Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden
Rudenhed, B:
Arvika Hosp, Dept Radiol, Arvika, Sweden
Nasr, SH:
Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA
Torres, VE:
Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA
Torra, R:
Fundacio Puigvert, Dept Nephrol, Barcelona, Spain
Bogdanova, N:
Univ Munster, Inst Human Genet, D-48149 Munster, Germany
Harris, PC:
Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA
Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
Green Published, Bronze
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