J Pediatr Genet 2019; 08(04): 235-239
DOI: 10.1055/s-0039-1692172
Case Report
Georg Thieme Verlag KG Stuttgart · New York

A Novel CLCN5 Splice Site Mutation in a Boy with Incomplete Phenotype of Dent Disease

Maria Bitsori
1  Department of Paediatrics, Heraklion University Hospital, Crete, Greece
2  Department of Paediatrics, School of Medicine, University of Crete, Heraklion, Crete, Greece
Emmanouil Galanakis
2  Department of Paediatrics, School of Medicine, University of Crete, Heraklion, Crete, Greece
› Author Affiliations
Further Information

Publication History

17 February 2019

22 April 2019

Publication Date:
04 June 2019 (online)


Dent disease is a rare X-linked renal proximal tubulopathy presenting with low-molecular-weight proteinuria (LMWP), hypercalciuria, and nephrocalcinosis, other signs of incomplete renal Fanconi syndrome, and renal failure. Early identification of patients who harbor disease-associated mutations is important for effective medical care and avoidance of unnecessary interventions. We report the case of an asymptomatic 9-year-old boy who presented with proteinuria in routine examination. Further investigation revealed the presence of nephrotic range proteinuria, mostly LMWP and mild hypercalciuria without nephrocalcinosis, or other features of tubular dysfunction. Renal function, growth, and bone mineral density were within regular limits. The male gender and the presence of LMWP and hypercalciuria even in the absence of other findings prompted us to genetic investigation for Dent disease. A novel splice site mutation (c.416–2A > G) of the chloride voltage-gated channel 5 (CLCN5) gene, responsible for Dent disease type 1 was identified. In silico analysis revealed that this mutation interferes with the mating of exons 4 and 5. Due to early molecular diagnosis, our patient did not undergo a renal biopsy, neither required aggressive pharmacological interventions. This case underscores the diversity and complexity of CLCN5 mutations and highlights the importance of early molecular testing in male patients with incomplete phenotype of Dent disease.


Informed consent was obtained from all individual participants included in the study.

Ethical Approval

Ethical approval was not applicable in our case.