Abstract
Dent disease is an X-linked tubulopathy caused by mutations affecting the voltage-gated chloride channel called ClC-5. Recently, it demonstrated that OCRL1 mutations can also cause not only Lowe syndrome but Dent disease. We have investigated 7 patients from 6 families diagnosed as Dent disease to elucidate the correlation between genotype and phenotype of Dent disease. In being diagnosed, all the patients show extremely high in low-molecular-weight proteinuria without apparent mental retardation or ocular abnormalities. All patients have been detected genetic mutations; three of them have CLCN5 and the others from three families OCRL1. Two CLCN5 mutations (nonsense and missense) and one OCRL1 (missense) were novel. After being diagnosed as Dent disease, two patients showed mental retardation mildly and they have OCRL1 mutations. Urinalysis and blood chemistry don't show Fanconi syndrome with renal tubular acidosis. Serum AST and LDH in patients with OCRL1 mutations were tend to be higher than those in patients with CLCN5 mutations. Two patients show renal dysfunction, one of which was the case of CLCN5 mutation.
We could detect genetic mutations of CLCN5 or OCRL1 in all 7 cases but couldn't clearly elucidate the genotype-phenotype correlation. The slight resemblance between Lowe syndrome and Dent disease with OCRL1 mutations suggests that we must reconsider the diagnostic criteria for both Lowe syndrome and Dent disease. Further studies are necessary to clarify pathophysiology about Dent disease.
