Hereditary sensory and autonomic neuropathy type II (Hereditary sensory and autonomic neuropathy type II) - Genes FAM134B and WNK1
Sensory and autonomic neuropathy type II hereditary (HSAN2) is a disease that primarily affects sensory neurons that transmit information about sensations such as pain, temperature and touch. In some people the disease can also cause mild abnormalities of the autonomic nervous system that controls involuntary body functions such as heart rate, respiration and digestion. Signs and symptoms of HSAN2 usually begin in infancy or early childhood.
The first sign is usually HSAN2 numbness in hands and feet. Shortly thereafter, affected individuals lose the ability to feel pain or temperature. Often these individuals develop ulcers on their hands and feet. Because affected individuals may not feel the pain of these injuries do not usually resort to immediate treatment. If left untreated, ulcers can become infected and can lead to amputation of the affected area. In addition, it is often unintentional self - harm, such as biting the tongue, lips or fingers. These injuries can lead to amputation of the affected areas. People usually have injuries and fractures in their hands, feet, limbs and joints untreated because of the inability to feel pain. Repeated injuries can lead to a condition known as Charcot joints, in which the bones and joints of the surrounding tissue are destroyed.
HSAN2 effects on the autonomic nervous system are more variable. Some newborns have problems with HSAN2 suction, which makes it difficult to eat. Furthermore, individuals can manifest HSAN2 apnea, digestive problems such as gastroesophageal reflux, slow flashing, weak deep tendon reflexes and fungiform papillae loss lingual.
They described two types of HSAN2, designated as HSAN2A and HSAN2B, each due to mutations in a different gene. The HSAN2A type is due to mutations in the WNK1 (WNK lysine deficient protein kinase 1) gene, while the HSAN2B type is due to mutations in the FAM134B (family with sequence similarity 134 member B) gene. Although two different genes are involved, the signs and symptoms of HSAN2A and HSAN2B are the same.
The WNK1 gene, located on the short arm of chromosome 12 (12p13.3), encoding multiple protein isoforms WNK1. The different isoforms WNK1 are important in several functions in the body, including regulating blood pressure and pain sensation. One of the isoforms is the full - length version, L-WNK1, found in cells throughout the body. Another isoform, KS-WNK1, is found only in the kidney cells. The L-WNK1 and KS-WNK1 proteins act as kinases, which are enzymes that change the activity of other proteins by adding a phosphate group in specific positions. The L-WNK1 and KS-WNK1 proteins regulate channels in the cell membrane that control the transport of sodium or potassium in and out of cells through processes reabsorption and secretion. L-WNK1 protein increases the reabsorption of sodium and potassium secretion decreases, whereas the KS-WNK1 protein has the opposite effect. Sodium and potassium are important for the regulation of blood pressure, and a balance of L-WNK1 protein and protein KS-WNK1 kidney helps maintain the correct concentrations of sodium and potassium for blood pressure and potassium concentration healthy. Another isoform encoded from WNK1 gene WNK1 / HSN2, is found in nerve cells, including sensory neurons. However, the function of WNK1 / HSN2 protein is unknown.
They have identified at least nine WNK1 gene mutations in people with HSAN2A. All these mutations lead to the synthesis of an abnormally short, nonfunctional protein. People with HSAN2A have a reduction in the number of sensory neurons; However, it is unclear how WNK1 / HSN2 abnormal protein results in the loss of sensory neurons. Mutations in the gene involved in HSAN2A WNK1 not seem to affect the isoforms L-WNK1 and KS-WNK1.
The FAM134B gene, located on the short arm of chromosome 5 (5p15.1), encodes an important survival of sensory neurons and autonomous protein. Sensory neurons transmit sensations like pain, touch and temperature. autonomic neurons help control involuntary body functions such as heart rate and blood pressure. Inside neurons, FAM134B protein is found in the Golgi apparatus. However, the function of the protein is unknown FAM134B. Some studies indicate that neurons in which absent the protein FAM134B are undergoing apoptosis. Mutations in the gene FAM134B are responsible HSAN2B form of the disease. These genetic changes may result in an abnormally short, nonfunctional protein. The absence of functional protein FAM134B causes neurons apoptosis undergo, reducing the total number of sensory and autonomic neurons. Loss of neurons leads to the signs and symptoms of HSAN2B.
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 hereditary sensory and autonomic neuropathy type II (HSAN2), by complete PCR amplification of the exons of FAM134B and WNK1 genes, 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).