barttin CLCNK type accessory beta subunit
The BSND gene provides instructions for making a protein called barttin. This protein is found primarily in the kidneys, where it attaches (binds) to two specific chloride channels: ClC-Ka (produced from the CLCNKA gene) and ClC-Kb (produced from the CLCNKB gene). The ClC-Ka and ClC-Kb channels transport charged atoms of chlorine (chloride ions) out of kidney cells.
Barttin is essential for the normal placement of ClC-Ka and ClC-Kb channels in the cell membrane. It also regulates the channels' stability and function. The transport of chloride ions is part of the mechanism by which the kidneys reabsorb salt (sodium chloride or NaCl) from the urine back into the bloodstream. The retention of salt affects the body's fluid levels and helps maintain blood pressure.
Barttin, ClC-Ka, and ClC-Kb are also found in the inner ear, where they play a role in normal hearing.
More than a dozen mutations in the BSND gene have been identified in people with Bartter syndrome type IV. This form of the disorder causes severe or life-threatening health problems that become apparent before or soon after birth. Affected individuals also have hearing loss caused by abnormalities in the inner ear, which is why Bartter syndrome type IV is also known as antenatal Bartter syndrome with sensorineural deafness.
BSND gene mutations impair barttin's ability to regulate the ClC-Ka and ClC-Kb channels. Some mutations keep the channels from ever reaching the cell membrane. Other mutations allow the channels to reach the cell membrane but prevent them from transporting ions properly. As a result, the kidneys cannot reabsorb salt normally and excess salt is lost through the urine (salt wasting). The abnormal salt loss disrupts the normal balance of ions in the body. This imbalance underlies many of the major features of Bartter syndrome, including a failure to grow and gain weight at the expected rate (failure to thrive), dehydration, constipation, and increased urine production (polyuria). A loss of ClC-Ka and ClC-Kb function in the inner ear is responsible for the hearing loss characteristic of Bartter syndrome type IV.
Genetics Home Reference provides information about nonsyndromic hearing loss.
- Bartter syndrome, infantile, with sensorineural deafness (Barttin)
- barttin CLCNK-type chloride channel accessory beta subunit
- deafness, autosomal recessive 73