Macrothrombocytopenia and progressive deafness syndrome ... (MYH9 related processes: May-Hegglin anomaly, Epstein syndrome Fechtner syndrome, Sebastian syndrome) (MYH9-related disorder) - Gen MYH9
Macrothrombocytopenia syndrome and progressive deafness is a process involving many signs and symptoms, so this set of affectations is called MYH9 related processes. The manifestations of genetic alterations MYH9 gene, include bleeding, hearing loss, renal disease, and cataracts. Bleeding due to thrombocytopenia, which in women can cause menorrhagia. In affected, platelets, but decreased in number, are larger, so do not move easily through the blood vessels of smaller diameter, making more difficult blood clotting. In some hearing loss exists affected by abnormalities in the inner ear (sensorineural hearing loss). Deafness may be present at birth or develop much later. About 30-70% of patients develop kidney disease, which usually starts in adults, the first sign of this involvement proteinuria and / or hematuria, by glomerular involvement, and eventually can lead to a failure renal. Some affected develop cataracts at the beginning of adulthood, increasing with the passage of time.
It should be borne in mind that not all affected by disorders related to MYH9 manifest all the signs and symptoms, so have differentiated, by some, as distinct entities (Anomaly May-Hegglin; Epstein syndrome; syndrome Fechtner, Sebastian syndrome), when knowing that the same genetic alteration are included in the same entity, with different possible manifestations.
The cause of this syndrome are mutations in the gene MYH9 (Myosin, heavy chain 9, non-muscle), located on the long arm of chromosome 22 (22q13.1). This gene belongs to the family of genes called "myosin superfamily" and encodes the "Myosin-9" protein, which is part of the protein myosin IIA. There are three forms of myosin II: myosin IIA, IIB myosin and myosin IIC. These three forms of myosin are by the body, and develop various functions such as cell motility, maintenance of cell shape, and cytokinesis, the process by the cytoplasm divides to give two cells. While some cells use more than one type of myosin II, some cells, such as platelets and leukocytes, only use myosin IIA, so that alteration of this form of myosin affects more the function of these cells.
Described more than 45 mutations MYH9 gene causing the synthesis of a nonfunctional protein myosin-9 can not interact with the other subunits of myosin IIA. Platelets and leukocytes which have only myosin IIA, are most affected, lacking functional myosin-9. As there myosin functional IIA, large immature blood platelets are released with an abnormal number of normal platelets. In leukocytes, myosin-9 is grouped abnormal, resulting in inclusion bodies can be observed in them. When mutations are closer to the head end of the protein, most obvious alterations that when mutations are found in the tail of the protein produced. Has been associated that the amino acid arginine at position 702, with major alterations, including very severe thrombocytopenia, renal disease and early - onset deafness in childhood.
This process is inherited as an autosomal dominant inheritance, which means that a single copy of the gene altered in each cell is sufficient to express the alteration. In most affected the process is inherited from one parent. In approximately 30% of cases the process is the result of new mutations, and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with macrothrombocytopenia and progressive deafness, by complete PCR amplification of exons MYH9 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).