Severe manifestation of Bartter syndrome Type IV caused by a novel insertion mutation in the BSND gene

Abstract

Bartter syndrome Type IV is a rare subtype of the Bartter syndromes that leads to both severe renal salt wasting and sensorineural deafness. This autosomal recessive disease is caused by mutations in the gene encoding barttin, BSND, an essential subunit of the ClC-K chloride channels expressed in renal and inner ear epithelia. Patients differ in the severity of renal symptoms, which appears to depend on the modification of channel function by the mutant barttin. To date, only a few BSND mutations have been reported, most of which are missense or nonsense mutations. In this study, we report the identification of the first insertion mutation, p.W102Vfs*7, in the BSND gene of a newborn girl with acute clinical symptoms including early-onset chronic renal failure. The results support previous data indicating that mutations that are predicted to abolish barttin expression are associated with a severe phenotype and early onset renal failure.

Mouse genetics reveals Barttin as a genetic modifier of Joubert syndrome

“…S3A). Bartter syndrome patients with BSND mutations have reduced urine-concentrating capacity, resulting in increased urine production (polyuria) and chronic kidney disease which may progress to ESRD (31,32), as do Joubert syndrome patients with renal involvement (nephronophthisis) (33,34). It is noteworthy that the mutations in CFTR encoding an apical chloride channel may also modify cystic kidney disease phenotypes in patients with autosomal dominant polycystic kidney disease, highlighting the importance of chloride transport in cyst expansion (35).…”

Multiple long runs of homozygosity detected by SNP array: offspring of consanguineous parents and his siblings

“…This autosomal recessive disease is caused by mutations in the gene encoding barttin, an essential subunit of the ClC-K chloride channels expressed in renal and inner ear epithelia. [8][9][10] This work report a case (S1) of a 20 years-old man with late onset presentation of Bartter syndrome Type IV and mild phenotype who had deafness, hypokalemia, erythrocytosis and secondary hyperparathyroidism. In summary, we have demonstrated that during the genetics evaluation of a patient affected by a rare disorder in the setting of consanguinity, SNP array analysis should be considered, except if the diagnosis is obvious.…”

BSND and ATP6V1G3

“… 40 Germline mutations of the BSND gene cause Bartter syndrome type IV, which is an autosomal recessive disease characterized by salt loss, hypokalemia, metabolic alkalosis, and sensorineural deafness. 41 At present, several research papers examining germline mutations of the BSND gene in the Bartter syndrome family have been reported; 42 however, the expression of BSND protein in RCC has not been previously reported. ATP6V1G3, another immunohistochemical marker identified in this study, is a subunit of vacuolar-H + ATPase that couples ATP hydrolysis to proton pumping across membranes.…”