Original Investigations: Pathogenesis and Treatment of Kidney Disease and HypertensionRecurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease★
Section snippets
TOR72 pedigree
In the course of ascertaining more than 250 ADPKD families for genetic studies, we identified a white family (TOR72) in which consanguinous marriage between affected first-degree cousins was clearly documented (III:2 and III:3, Fig 1).
Results
Three of the affected members of TOR72 (ie, III:2, III:3, and III:4) developed end-stage renal disease at 58, 66, and 59 years of age, respectively. Disease severity in these individuals was typical of type 1 ADPKD.17 This clinical impression was confirmed by pairwise linkage results (Table 1), which were consistent with linkage to PKD1 (Zmax = 1.66, θ = 0.00 for KG8), but not PKD2 (Zmax = −2.54, θ = 0.00 for SPP1).
Discussion
Given that ADPKD affects between 1 in 500 to 1,000 live births, bilineal disease is predicted to occur in approximately 1 in 250,000 to 1,000,000 marriages in the general population.17, 18 This likelihood is increased further in populations in which consanguinous marriage is prevalent. A potential consequence of bilineal ADPKD is that some of the affected members from these pedigrees may carry two germline mutations. Two scenarios may result. First, in families in which germline mutations of
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Supported in part by the Kidney Foundation of Canada.
Address reprint requests to York Pei, MD, 13 EN-228, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4. E-mail: [email protected]
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