Instituto Valenciano de Microbiología
(IVAMI)

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
Email: 
www.ivami.com
CIF B-96337217

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Distal renal tubular acidosis with deafness syndrome ..., (Renal tubular acidosis With deafness syndrome) - Genes and ATP6V1B1 ATP6V0A4.

Renal tubular acidosis with deafness is a process characterized by kidney problems and hearing loss. In affected individuals, the kidneys can not adequately remove acidic metabolites body and acidified blood pH, causing a chemical imbalance called metabolic acidosis. This imbalance can result in a series of signs and symptoms vary in severity.

Often, metabolic acidosis causes nausea, vomiting and dehydration. The inability to remove acid metabolites of the body often causes slow growth and rickets in children and osteomalacia in adults. This bone disorder characterized by bone pain, bowlegged and difficulty walking. Rarely, people affected manifest episodes of hypokalemic paralysis. In addition, affected individuals have sensorineural hearing loss and inner ear abnormality called dilated vestibular aqueduct. The vestibular aqueduct is a bony canal that runs from the inner ear to the temporal bone of the skull to the brain; however, the relationship between dilated vestibular aqueduct and hearing loss is unclear. In renal tubular acidosis with deafness, dilated vestibular aqueduct usually occurs in individuals whose hearing loss begins in childhood.

Renal tubular acidosis with deafness is due to mutations in genes ATP6V0A4, located on the long arm of chromosome 7 (7q34) and ATP6V1B1, located on the long arm of chromosome 2 (2p13.1). These genes encode proteins which are subunits of a large protein complex known as vacuolar H + -ATPase (V-ATPase). V-ATPases are the group of similar complexes which act as pumps to move atoms positively charged hydrogen through the membranes. Since acids are substances that can "donate" protons to other molecules, this movement of protons helps regulate the pH of the cells and their environment. Strict control of pH for most biological reactions necessary to proceed correctly. The V-ATPase, including subunits produced from the ATP6V1B1 and ATP6V0A4 genes found in the inner ear and nephrons. Each nephron has two parts: a renal corpuscle or glomerulus that filters blood, and renal tubule reabsorbs substances that are necessary, and removes substances that are not necessary in the urine. The V-ATPase is involved in regulating the amount of acid that is removed from the blood in the urine, and also to maintain the proper pH of the fluid in the inner ear (endolymph).

They have identified at least 25 mutations in the gene ATP6V1B1 and several mutations in the gene ATP6V0A4 in people with renal tubular acidosis with deafness. Mutations in the ATP6V0A4 or ATP6V1B1 gene alter the functioning of complex V-ATPase and reduce the body's ability to control the pH of the blood and the fluid in the inner ear, resulting in the signs and symptoms of renal tubular acidosis with deafness.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome distal renal tubular acidosis with deafness, by complete PCR amplification of the exons of ATP6V0A4 and ATP6V1B1, respectively, and subsequent sequencing genes.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).

which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with syndrome distal renal tubular acidosis associated with SLC4A1, by complete PCR amplification of exons SLC4A1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).