Aberrant PKD2 splicing due to a presumed novel missense mutation in autosomal-dominant polycystic kidney disease.
Autosomal-dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder characterized by abnormal proliferation of renal tubular epithelium, leading to massive kidney enlargement and progressive chronic kidney disease. ADPKD is caused by mutations in PKD1 and PKD2 genes. Herein, we describe and characterize a novel missense mutation in the PKD2 gene (c.1320G>T) in a 41-year-old White man with kidney cysts and a family history of ADPKD. This mutation abolishes a conserved acceptor splice site of intron 5, resulting in a premature termination following the addition of three aberrant amino acids (PKD2 p.L441C fsX4). We demonstrate that the aberrantly spliced transcript is found in substantial amounts in the patient's peripheral blood leukocytes (PBL), and show that this alternative splicing of exon 6 occurs, to a lesser magnitude, in other patients with ADPKD and in normal control individuals. The biological and clinical significance of this splice variant in ADPKD is currently unknown.
Departments of Pathology and Laboratory Medicine Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Y-C
YC
Tan
J
J
Blumenfeld
A
A
Michaeel
S
S
Donahue
M
M
Balina
T
T
Parker
D
D
Levine
H
H
Rennert
D000328:Adult; D003560:Cysts / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D022821:RNA Splice Sites; D012326:RNA Splicing; D050396:TRPP Cation Channels / Q000235:genetics* / Q000378:metabolism; D014463:Ultrasonography
D022821:RNA Splice Sites; D050396:TRPP Cation Channels