A Novel Heterozygous Deletion Variant in KLOTHO Gene Leading to Haploinsufficiency and Impairment of Fibroblast Growth Factor 23 Signaling Pathway.

ABSTRACT: Hyperphosphatemia is commonly present in end-stage renal disease. Klotho (KL) is implicated in phosphate homeostasis since it acts as obligate co-receptor for the fibroblast growth factor 23 (FGF23), a major phosphaturic hormone. We hypothesized that genetic variation in the KL gene might be associated with alterations in phosphate homeostasis resulting in hyperphosphatemia. We performed sequencing for determining KL gene variants in a group of resistant hyperphosphatemic dialysis patients. In a 67-year-old female, blood DNA sequencing revealed a heterozygous deletion of a T at position 1041 (c.1041delT) in exon 2. This variation caused a frameshift with substitution of isoleucine for phenylalanine and introduction of a premature termination codon (p.Ile348Phefs*28). cDNA sequencing showed

SUBMITTER: Martin-Nunez E 

PROVIDER: S-EPMC6517886 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature