ARE MOTHERS OF BOYS WITH DENT’S DISEASE ASYMPTOMATIC CARRIERS FOR X-LINKED TUBULAR DISORDER?

Dent’s disease is an X-linked proximal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and progression to chronic kidney failure. The disease is caused by mutations in CLCN5 or OCRL genes and affects males, whereas female carriers are generally asymptomatic. THE AIM: to study phenotype and genotype of patients’ mothers with Dent’s disease to exclude asymptomatic carrier of CLCN5 or OCRL gene mutations responsible for X-linked tubulopathy development. PATIENTS AND METHODS. We conducted clinical and molecular-genetic study of 9 mothers of 10 boys with Dent’s disease from 8 unrelated families. Direct Sanger sequencing of CLCN5 and OCRL genes were carried out with genomic DNA of all patients and their mothers. RESULTS. Carrier status of Dent’s disease 1 (n=7) and 2 types (n=2) was confirmed in all patients’ mothers. The most prevalent features of Dent’s disease in probands’ mothers were decrease in phosphate reabsorption, hypophosphatemia, medullary nephrocalcinosis and progression to CKD 2 stage. Low molecular weight proteinuria and hypercalciuria were rare revealed in carrier females. Full phenotype of Dent’s disease discovered in 2 cousins females carrier for Dent’s disease 1 type. CONCLUSION. We found that all carrier females had phenotypic variation of Dent disease’ symptoms. We speculate that revealed phenotype in carrier females for Dent disease might be a consequence of autosome translocation or nonrandom X chromosome inactivation. These data suggest that clinicians should consider a diagnostic evaluation of mothers of boys with Dent’s disease to determine phenotype and early prevention of progression to chronic kidney disease.

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