LGR4/GPR48 inactivation leads to aniridia-genitourinary anomalies-mental retardation syndrome defects.

[aniridia]

AGR syndrome (the clinical triad of aniridia , genitourinary anomalies , and mental retardation , a subgroup of WAGR syndrome for Wilm 's tumor , aniridia , genitourinary anomalies , and mental retardation ) is a rare syndrome caused by a contiguous gene deletion in the 11 p 13 -14 region . However , the mechanisms of WAGR syndrome pathogenesis are elusive . In this study we provide evidence that LGR 4 (also named GPR 4 8 ), the only G-protein-coupled receptor gene in the human chromosome 11 p 12 -11 p 14 .4 fragment , is the key gene responsible for the diseases of AGR syndrome . Deletion of Lgr 4 in mouse led to aniridia , polycystic kidney disease , genitourinary anomalies , and mental retardation , similar to the pathological defects of AGR syndrome . Furthermore , Lgr 4 inactivation significantly increased cell apoptosis and decreased the expression of multiple important genes involved in the development of WAGR syndrome related organs . Specifically , deletion of Lgr 4 down-regulated the expression of histone demethylases Jmjd 2 a and Fbxl 10 through cAMP-CREB signaling pathways both in mouse embryonic fibroblast cells and in urinary and reproductive system mouse tissues . Our data suggest that Lgr 4 , which regulates eye , kidney , testis , ovary , and uterine organ development as well as mental development through genetic and epigenetic surveillance , is a novel candidate gene for the pathogenesis of AGR syndrome .

Diseases
Validation

Diseases presenting "polycystic kidney disease" symptom

aniridia

heparin-induced thrombocytopenia

primary hyperoxaluria type 1

This symptom has already been validated