A novel mutation associated with Type III Bartter syndrome: A report of five cases

Abstract

The clinical, biochemical and mutation spectra of Chinese patients with Type III Bartter syndrome (type III BS), a rare autosomal recessive disorder, were investigated. A total of five unrelated Chinese patients aged 8 months to 24 years were diagnosed with type III BS via analysis of biochemical markers, including chloride, potassium and calcium, and genetic sequencing. The levels of insulin-like growth factor-1 (IGF-1) were evaluated via ELI SA and a mutation study of cultured amniocytes was conducted for prenatal diagnosis. The child patients were admitted for polydipsia, polyuria, myasthenia and developmental delay, whereas the adult patients were hospitalized for limb numbness, polydipsia and polyuria. Nine variants in the chloride voltage-gated channel Kb (CLCNKB) gene were detected, including eight sequence variants and one whole CLCNKB gene deletion. One sequence variant (c.1967T>C) was novel, whereas the remaining variants (c.595G>T, c.908A>C, c.1004T>C, c.1312C>T, c.1334_1335delCT and c.1718C>A) and the whole gene deletion had been previously reported. The whole gene deletion was frequently observed in patients with early-onset type III BS in the present study. Two patients showed IGF-1 deficiency with normal growth hormone level. All patients were treated with potassium supplementation and indometacin. The mother of one patient underwent amniocentesis during her second pregnancy; the fetus was not affected by type III BS based on screening for sequence variants, and normal development and blood electrolyte analysis following birth confirmed the diagnosis. In conclusion, five cases of type III BS in patients from mainland China were reported. Large deletions were frequently detected, particularly in early-onset patients; isolated IGF-1 deficiency was found, one novel sequence variant was identified. Prenatal diagnosis was successfully established using genetic analysis of cultured amniocytes, and may facilitate the prevention of congenital defect of type III BS in the next pregnancy.