Andermann syndrome ..., (Agenesis of Corpus Callosum with Peripheral Neuropathy) (Andermann syndrome) - SLC12A6 Gene
Andermann syndrome is a genetic disorder that affects the nerves so the transmission of signals for sensitivity and muscle movement is affected. Therefore it is a motor and sensory neuropathy, which in most cases is presented along with agenesis of the corpus callosum brain. As a result, those affected by Andermann syndrome have abnormal or absent reflexes (areflexia) and muscle weakness (hypotonia). Furthermore, they have loss of muscle mass, progressive weakness, tremors and loss of sensation in the extremities. In severe cases, affected individuals develop scoliosis may require surgery. Children usually start walking at 3 or 4 years and as they grow, they restrict the movement of certain joints until, in adolescence, stop walking. In addition, Andermann syndrome may be related to the extension of certain cranial nerves, which can lead to mental retardation, facial muscle weakness, drooping eyelids and gaze palsy. Also, some people with Andermann syndrome have atypical physical characteristics such as ocular hypertelorism, brachycephaly and syndactyly. The Andermann syndrome is associated with lower life expectancy, but affected individuals often live to adulthood.
Localized mutations in SLC12A6 gene are responsible for Andermann syndrome. The SLC12A6 gene, located on the long arm of chromosome 15 (15q13), prtenece family of K-Cl cotransporter. The proteins encoded by this gene is activated by inflammation induced under hypotonic conditions. Its function is to decrease intracellular chloride concentrations below the potential of electrochemical equilibrium. The specific function cotransporter encoded by the SLC12A6 gene is not entirely known, but seems to be crucial for the development and maintenance of nerve tissue and is believed to be involved in the regulation of the amounts of potassium, chloride and water into the cells and intercellular spaces.
They have identified at least 6 SLC12A6 gene mutations in people with the syndrome Andermann. Almost all affected individuals of French Canadian descent have the same mutation in both copies of SLC12A6 gene, in which the guanine nucleotide is eliminated in the 2436 position (2436delG). This mutation is common in populations of the regions of Saguenay-Lac-Saint-Jean and Charlevoix northeastern Quebec. Mutations in the SLC12A6 gene associated Andermann syndrome disrupt protein function cotransportadora, interrupting and / or altering the development of the corpus callosum and maintenance of the nerves involved in signaling movement.
This disease is inherited in an autosomal recessive pattern, that is, 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 Andermann syndrome by complete PCR amplification of exons SLC12A6 gene, and subsequent sequencing. We recommend starting the study depending on the origin of the patient, as have been reported mutational differences depending on the source. For patients of European and Canadian origin, it is recommended to start by exons 11, 15 and 18, where the main mutations found so far are located.
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).