William Wong1, Gemma Poke2, Maria Stack3, Tonya Kara3, Chanel Prestidge3, Kim Flintoff4. 1. Department of Paediatric Nephrology, Starship Children's Hospital, Private Bag 92024, Park Road, Auckland, New Zealand. wwong@adhb.govt.nz. 2. Genetic Health Service New Zealand Central Hub, Wellington, New Zealand. 3. Department of Paediatric Nephrology, Starship Children's Hospital, Private Bag 92024, Park Road, Auckland, New Zealand. 4. Wellington Regional Genetics Laboratory, Wellington, New Zealand.
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.
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: S E Lloyd; W Gunther; S H Pearce; A Thomson; M L Bianchi; M Bosio; I W Craig; S E Fisher; S J Scheinman; O Wrong; T J Jentsch; R V Thakker Journal: Hum Mol Genet Date: 1997-08 Impact factor: 6.150
Authors: Radovan Bogdanović; Markus Draaken; Alma Toromanović; Maja Dordević; Natasa Stajić; Michael Ludwig Journal: Pediatr Nephrol Date: 2010-08-01 Impact factor: 3.714