Progressive myoclonus epilepsy with ataxia related to PRICKLE1 (progressive myoclonus epilepsy related PRICKLE1- With ataxia) - Gen PRICKLE1.

Progressive myoclonic epilepsy with ataxia related to PRICKLE1 is a rare inherited disorder characterized by epilepsy and problems with movement. In general, the signs and symptoms of this disorder begin between 5 and 10 years old. The first symptoms include ataxia. Often, affected children have difficulty walking. His gait is unbalanced and may fall frequently. Later, these children develop myoclonus, which causes additional problems with movement and can also affect the muscles of the face, resulting in dysarthria. Some affected individuals develop tonic-clonic seizures. These attacks involve a loss of consciousness, muscle rigidity and convulsions. They often occur at night during sleep. This disease does not seem to affect intellectual ability. Although some affected individuals have died in childhood, many have lived to adulthood.

This process is due to mutations in the gene PRICKLE1, located on the long arm of chromosome 12 (12q12). This gene encodes a protein called prickle-1. The function of this protein is unclear, but seems to play an important role in the development of the nervous system. Prickle-1 is probably part of a signaling pathway chemical known as canonical Wnt signaling no. During development before birth, Wnt noncanonical helps determine the position of various components within cells. This pathway also regulates the movement of neurons in the developing nervous system. Studies suggest that the protein interacts with other proteins, including factor REST. The REST protein regulates several critical genes in neurons suppressing activity. To regulate these genes, REST must enter the core and attached to specific regions of DNA. Is not yet clear how the interaction between prickle REST-1 and contributes to the normal development of the nervous system.

They have identified at least three mutations in the gene PRICKLE1 in people with progressive myoclonus epilepsy with ataxia related to PRICKLE1. Each mutation changes a single amino acid in the prickle-1 protein. One of the known mutations seems to interrupt the interaction between prickle-1 and REST, REST blocking transport out of the nucleus. Consequently, REST inappropriately can suppress certain genes in the developing nervous system. It is unclear how mutations in the gene PRICKLE1 lead to movement problems, seizures and other features of the disease.

Some cases of progressive myoclonus epilepsy with ataxia related PRICKLE1 are 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. Other cases of the disease are considered autosomal dominant because a copy of the altered gene in each cell is sufficient for alteration is expressed. These cases are caused by 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 progressive myoclonus epilepsy with ataxia related PRICKLE1 by the complete PCR amplification of the gene exons PRICKLE1, 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).