Inclusion of microvilli, disease ... (Microvillus inclusion disease) - Gen MYO5B.

The microvilli inclusion disease is a chronic disease characterized by watery diarrhea, which is usually potentially lethal from the first hours or days of life. Rarely, diarrhea begins around 3 or 4 months old. Food intake increases the incidence of diarrhea.

The disease prevents the absorption of nutrients from food during digestion, leading to malnutrition and dehydration. Affected children usually have stunted growth, developmental delay, liver and kidneys, and osteoporosis. Some affected individuals develop cholestasis leading to cirrhosis. In affected individuals, parenteral nutrition is necessary for life. Even with nutritional supplements, most children do not survive beyond infancy. A variant of the disease with mild diarrhea, often parenteral nutrition does not require full time. People with this variant tend to live up to past childhood.

This process is due to mutations in the gene MYO5B located the long arm of chromosome 18 (18q21). This gene encodes the protein myosin Vb. Myosins are involved in cell movement and transport of materials within and between cells. Myosin Vb helps determine the position of various components within cells. Furthermore, this protein plays a role in the movement of the components of the cell membrane into the cell for recycling.

They have been recognized more than 40 mutations in the gene give rise MYO5B the inclusion disease microvilli. These mutations lead to decreased or absent function myosin Vb. In enterocytes, deficiency in the function of myosin Vb changes cell polarity. As a result, the enterocytes can not properly form their microvilli. Within enterocytes affected, small groups of abnormal microvilli are mixed with digestive proteins leading to the formation of microvilli inclusions, which contribute to the dysfunction of enterocytes. Disorganized enterocytes with microvilli malformed reduce the ability of the intestine to absorb nutrients and fluids. The inability to absorb nutrients and fluids during digestion causes severe diarrhea, malnutrition and dehydration in people with inclusion of microvilli disease.

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 inclusion of microvilli disease by the complete PCR amplification of exons MYO5B gene, 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).