Mutation G47R in the BSND gene causes Bartter syndrome with deafness in two Spanish families.
Bartter syndrome (BS) is a heterogeneous group of autosomal recessive hypokalaemic salt-losing tubulopathies. Five types of BS caused by different genetic defects have been identified, and one of them is associated with sensorineural deafness (BSND). Mutations in the recently described BSND gene, mapped in chromosome 1p31, have been reported to be associated with BSND. This gene encodes barttin, an essential beta-subunit subunit for ClC-Ka and ClC-Kb channels. Both subunits are co-expressed in basolateral membranes of renal tubules, in the ascending limb of the loop of Henle, and in the stria vascularis of the inner ear. We studied two apparently unrelated Spanish families from the Canary Islands, with five members showing this pathology. Sequence analysis of the BSND gene showed that the affected members were homozygous for a C-to-T transition in exon 1, while their parents were heterozygous. This alteration results in a missense mutation, G47R, which has been previously shown to abolish the stimulatory effect on the subunit barttin of the ClC-Kb channel. Our results indicate that families with the G47R mutation indeed present polyhydramnios, premature birth and salt loss. Nevertheless, glomerular filtration rate was normal in all patients. Clinical manifestations are moderate in patients with the G47R mutation compared to other published data form patients with BSND. This constitutes the first report of BSND cases in Spain.
García-Nieto
Víctor
V
Unidad de Investigación-Asociada al Centro de Investigaciones Biológicas (CSIC), Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain. vgarcia@comtf.es
Flores
Carlos
C
Luis-Yanes
Maria I
MI
Gallego
Eduardo
E
Villar
Jesús
J
Claverie-Martín
Félix
F
D000293:Adolescent; D000328:Adult; D001477:Bartter Syndrome / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology; D003638:Deafness / Q000235:genetics; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D013030:Spain
C440005:BSND protein, human; C412733:CLCNKB protein, human; D018118:Chloride Channels; D008565:Membrane Proteins