Marinesco-Sjögren syndrome ... (Marinesco-Sjögren syndrome) - Gen SIL1.

The Marinesco-Sjögren syndrome is a disorder with a variety of signs and symptoms that affect many tissues. These signs and symptoms may include cataracts, which usually develop shortly after birth or in early childhood, myopathy, ataxia, further deterioration of muscle function in the future, mild to moderate mental retardation, short stature, scoliosis, strabismus, nystagmus and dysarthria. In addition, those affected may have hypogonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, affected individuals are delayed puberty or fail to have it.

The Marinesco-Sjögren syndrome is due to mutations in the gene SIL1, located on the long arm of chromosome 5 (5q31). This gene encodes a protein located in the endoplasmic reticulum. Among its many functions, the endoplasmic reticulum folds and modifies the newly formed to have the correct three - dimensional shape proteins. The protein SIL1 works with BiP, a protein that helps the folding newly encoded and properly refolded protein damaged proteins. To initiate this process, the aggregates BiP bind to a molecule of adenosine adenosine (ATP). When folded BiP protein, ATP becomes adenosine diphosphate (ADP). SIL1 then releases ADP BiP protein that can bind to another molecule of ATP and reactivate the process of protein folding. Because of its role, the SIL1 protein is considered a nucleotide exchange factor.

They described more than 12 mutations in the gene responsible SIL1 Marinesco-Sjögren syndrome. Most of these mutations lead to encoding a protein that has little or no activity. SIL1 a defective protein can not eliminate ADP BiP, so Bip becomes unable to bind ATP and restart the process of protein folding. A disruption in protein folding impairs the transport of proteins and causes the proteins to accumulate in the endoplasmic reticulum. This accumulation creates damages and destroys cells in many different tissues, leading to poor coordination, muscle weakness and other characteristics of Marinesco-Sjögren syndrome.

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 Marinesco-Sjögren syndrome of, by complete PCR amplification of the exons of the gene SIL1, 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).