Recurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease.
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian disorder that affects approximately 1 in 500 to 1,000 live births. Mutations in one of two genes, PKD1 and PKD2, account for the disease in most ADPKD families. Despite the relative high frequency of PKD1 mutant alleles, compound heterozygotes or diseased homozygotes have not been described.


RESULTS
We report a family with type 1 ADPKD in which the marriage between affected first-degree cousins resulted in two live-born heterozygous offspring and two fetuses lost in late pregnancy. Genetic analysis with PKD1 and PKD2 flanking markers showed that this family is PKD1 linked (z(max) = 1.66 and -2.54 at thetas = 0.0 for intragenic markers for PKD1 [ie, KG8] and PKD2 [ie, SPP1], respectively).


CONCLUSIONS
Given a 25% chance for mutant homozygosity in the offspring of this family, our findings suggest that homozygosity of PKD1 mutations in humans is embryonically lethal, as recently documented in Pkd1 knockout mice.
Paterson
Andrew D
AD
Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Wang
Kai Rong
KR
Lupea
Doina
D
St George-Hyslop
Peter
P
Pei
York
Y
D000026:Abortion, Habitual / Q000209:etiology* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003241:Consanguinity; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications* / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D050396:TRPP Cation Channels
D005819:Genetic Markers; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels