Phenotypic variability of Dent disease in a large New Zealand kindred.

Abstract

BACKGROUND:

Dent disease 1 is a rare cause of chronic kidney disease (CKD) in childhood secondary to mutations in the gene encoding the chloride-proton exchanger, CLC-5, which is found mainly in the proximal tubule. Clinical manifestations are variable and there are no known genotype-phenotype correlations.

CASE DIAGNOSIS/TREATMENT:

The proband was identified as having a mutation in CLCN5. The extended family of the proband was invited to participate in a study of Dent disease after several males were noted to have a history of CKD. Urine retinol binding protein, urine calcium, serum creatinine, and DNA samples were collected for analysis. Ten hemizygous males and 6 heterozygous females were identified. Advanced CKD was detected in 3 males (1 child). Renal biopsies in 4 children showed both glomerular and tubulo-interstitial changes. There was no correlation between age and disease severity.

CONCLUSIONS:

This is the first reported family from the southern hemisphere with this condition. A novel CLCN5 mutation is described, c.1618G>C (p.Ala540Pro). The severity of renal disease varies greatly among individuals.

• Authors: William Wong, Gemma Poke, Maria Stack, Tonya Kara, Chanel Prestidge, Kim Flintoff
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 32 Issue 2 Pg. 365-369 (02 2017) ISSN: 1432-198X [Electronic] Germany
• PMID: 27699523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLC-5 chloride channel
• Chloride Channels

Topics

• Adolescent
• Adult
• Aged
• Child
• Child, Preschool
• Chloride Channels (genetics)
• Female
• Genetic Diseases, X-Linked (diagnosis, genetics, physiopathology)
• Humans
• Hypercalciuria (urine)
• Kidney Calculi (diagnostic imaging, etiology)
• Male
• Middle Aged
• Mutation, Missense
• Nephrolithiasis (diagnosis, genetics, physiopathology)
• New Zealand
• Phenotype
• Proteinuria (urine)
• Renal Insufficiency, Chronic (etiology)
• Ultrasonography