Lissencephaly with cerebellar hypoplasia (lissencephaly cerebellar hypoplasia With) - Genes and TUBA1A RELN.
Lissencephaly with cerebellar hypoplasia (LCH) is a disorder that affects brain development causing lissencephaly. In addition, the part of the brain that coordinates movement is unusually small and underdeveloped (cerebellar hypoplasia). Often in those affected, other parts of the brain are also poorly developed including the hippocampus, which plays a role in learning and memory and the brain stem.
Some of the signs and symptoms of the disease include mental retardation, developmental delay and little or no communication skills. Some people affected have hypotonia, ataxia, difficulty sitting or standing unsupported, epilepsy, myopia, nystagmus and lymphedema.
This disease is due to mutations in the genes RELN and TUBA1A.
The RELN gene, located on the long arm of chromosome 7 (7q22), encodes a protein called reelin. In the developing brain, Reelin activates a signaling pathway that activates neurons to migrate to their proper places. After birth, Reelin probably plays a role in many processes in the brain, including the extension of axons and dendrites, which are essential for the transmission of nerve impulses. Reelin can also regulate synaptic plasticity between neurons. Furthermore, this protein controls the release of neurotransmitters. They have identified at least six mutations in the gene causing RELN lissencephaly with cerebellar hypoplasia. Genetic mutations leading to the lack of protein. As a result, the signaling pathway triggers neuronal migration is not activated, which leads to disorganization of neurons, no formation of folds and grooves in the brain and improper development of the brain structures. This alteration of brain development causes mental retardation, developmental delay, movement problems and other signs and symptoms of the disease.
The TUBA1A gene, located on the long arm of chromosome 12 (12q13.12), encodes a protein called alpha-tubulin. This protein is part of the family of proteins tubulin forming microtubules and organize comprising the cytoskeleton. Microtubules are composed of ?-tubulin and a similar protein called ?-tubulin (encoded by a different gene). Microtubules are necessary for cell division and movement. Proteins tubulin forming microtubules move from one end of a microtubule to the other end. This protein transfer drives microtubules in a specific direction, moving the cell. They have identified at least 10 mutations in the gene TUBA1A causing disease, and characterized by amino acid changes in the ?-tubulin protein. While these altered proteins can be incorporated into microtubules, it is believed that these microtubules have reduced function or abnormal function. In the developing brain, a deterioration in the function of microtubules results in the absence of formation of folds and furrows in the brain and improper development of brain structures. This alteration of brain development causes mental retardation, developmental delay, movement problems and other signs and symptoms of the disease.
When the disease is caused by mutations in the RELN gene 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. When the disease is caused by mutations in the TUBA1A gene is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the alteration. Most of these cases are the result of new mutations in the gene and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with lissencephaly with cerebellar hypoplasia, by complete PCR amplification of the exons of RELN and TUBA1A genes, respectively, 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).