Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


5q minus syndrome ... (5q minus syndrome) - Genes MIR145, MIR146A, RPS14 and chromosome 5.

5q minus syndrome is a rare type of alteration of the bone marrow called myelodysplastic syndrome (MDS). The MDS comprises a group of diseases in which immature blood cells fail to develop normally, resulting in an excess of immature cells and a deficiency of normal mature blood cells.

5q minus syndrome, the development of erythrocytes is particularly affected, leading to anemia. Furthermore, erythrocytes are present are macrocytic. Although many people with 5q minus syndrome manifest not related anemia, especially in the early stages of the disease, symptoms some affected individuals manifest fatigue, weakness and pallor as the disease progresses. In addition, affected individuals have an abnormal development of megakaryocytes. A common finding in affected persons is the presence of abnormal cells as described hypolobulated megakaryocytes. In addition, some individuals have an excess of platelets, while others have normal platelet counts. Likewise, some affected individuals may develop acute myeloid leukemia (AML). Progression to AML occurs less frequently in people with 5q minus syndrome than in those with other forms of MDS.

People usually have 46 chromosomes in every cell, divided into 23 pairs. Among them are two copies of chromosome 5, one copy inherited from each parent. Chromosome 5 has 181 million base pairs, represents about 6% of total DNA in cells, and contains approximately 900 genes encoding proteins. These proteins perform a variety of different functions in the body. Genes on chromosome 5 are among the approximately 20,000 to 25,000 total genes in the human genome.

5q minus syndrome is caused by removing a DNA region of long arm of chromosome 5. In most affected people missing a sequence of about 1.5 megabases (Mb). However, the size of the deleted region varies. This deletion occurs in immature blood cells during the life of a person and affects one of the two copies of chromosome 5 in each cell. Commonly deleted region of DNA contains 40 genes, many of which play a critical role in normal development of blood cells. It is believed that the loss of multiple genes in this region contributes to the characteristics of the syndrome. Of these genes, the most critical would be the RPS14 gene (whose loss results in the characteristic problems with the development of erythrocytes) and MIR145 and MIR146A genes (whose loss contributes to abnormalities of megakaryocytes and platelets, and may promote excessive growth immature cells). It is determining how the loss of other genes in the deleted region could be involved in the characteristics of 5q minus syndrome.

The MIR145 genes located on the long arm of chromosome 5 (5q32), and MIR146A, located on the long arm of chromosome 5 (5q34), encoding microRNA-145 (miR-145) and microRNA-146a (miR-146a), respectively. MicroRNAs (miRNAs) are short stretches of RNA. These molecules regulate gene expression by blocking the protein coding process. MiR-145 and miR-146a are abundant in immature blood cells and control the expression of hundreds of genes. It is believed that these microRNAs are involved in the development of normal blood cells. In particular, they appear to play a role in the growth and division of megakaryocytes, which produce platelets. The loss of a copy of both the gene and the MIR146A MIR145 gene reduces the amount of miR-145 and miR-146a in cells. As a result, the concentrations of proteins whose coding is normally blocked by miR-145 and miR-146a are raised, leading to abnormal development of megakaryocytes produced in the 5q minus syndrome.

The RPS14 gene, located on the long arm of chromosome 5 (5q31-q33), encoding one of the 80 different about ribosomal proteins, components of ribosomes. Ribosomes processed cell genetic instructions to encode proteins. Each ribosome consists of two subunits, large and small. The protein encoded from the RPS14 gene is one of those found in the small subunit. The specific functions of the protein and other RPS14 ribosomal proteins within these subunits are unclear. Some ribosomal proteins are involved in the assembly or stability of the ribosomes. Others help carry out the main function of the ribosome in the synthesis of new proteins. Probably some ribosomal proteins may have other functions, such as participation in chemical signaling pathways inside the cell, the regulation of cell division and cell apoptosis control. The loss of a copy of the RPS14 gene reduces the amount of protein that is encoded RPS14. It is believed that the ribosomal proteins deficiency in operation increases apoptosis of the cells forming blood in the bone marrow, resulting in anemia.

This disease usually not inherited but arises from a somatic mutation in body cells that occurs after conception. Affected individuals usually have no history of the disease in his family.

Tests in IVAMI: in IVAMI carry the genetic study of chromosome 5, to see if there are deletions or loss of genes involved in this syndrome.

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).