Dyserythropoietic Anemia Types I and II

(Congenital dyserythropoietic anemia types I and II) - Genes and SEC23B CDAN1.

Dyserythropoietic congenital anemia (CDA) is an inherited blood disorder that affects the development of red blood cells. This alteration is one of the many types of anemia characterized by decreasing red blood cells. This reduction prevents blood carry adequate oxygen to body tissues. The resulting symptoms can include fatigue, weakness, pale skin, and other complications. We have identified three main types of CDA: type I, type II and type III. All types have genetic causes and patterns of different signs and symptoms.

Type I disease, it is characterized by moderate to severe anemia. Usually diagnosed in childhood or adolescence, although in some cases, the condition can be detected before birth. Many people affected with jaundice and hepatomegaly. This alteration also causes the body to absorb too much iron, which accumulates and can damage tissues and organs. In particular, iron overload can lead to arrhythmias, congestive heart failure, cirrhosis and diabetes. Rarely, people with type I are born with skeletal abnormalities that most often affects the fingers and / or feet.

Anemia associated with type II disease can vary from mild to severe. The most affected people have jaundice, hepatosplenomegaly and gallstones. This form of the disease is usually diagnosed in adolescence or early adulthood. Overall, after 20 years, an abnormal accumulation of iron leads to complications such as heart disease, diabetes and cirrhosis occurs.

Signs and symptoms of type III tend to be milder than those of other types. Most affected individuals have hepatosplenomegaly and iron does not accumulate in tissues and organs. In adulthood, abnormalities of the retina can cause vision problems. Some people with Type III disease have monoclonal gammopathy, which can lead to multiple myeloma.

This disease is due to mutations in genes CDAN1 and SEC23B. Type I disease is usually caused by mutations in the gene CDAN1. Type II can be caused by mutations in either of these two genes. The genetic cause of type III has not been identified, but is believed to be a result of mutations in a position located in the 15q22 gene.

The CDAN1 gene, located on the long arm of chromosome 15 (15q15.2), encoding codanina-1 protein. Although this protein is present in cells throughout the body, it is known very little about its function. It is believed that codanina-1 is associated with heterochromatin DNA form plays an important role in maintaining the structure of the cell nucleus. It is thought that codanina-1 protein may be involved in the process of erythropoiesis, through which the formation of red blood cells occurs. More specifically, this protein may play a key role in the organization of heterochromatin during the division of these cells in development.

Have identified more than 30 mutations in the gene CDAN1 in persons with congenital dyserythropoietic anemia (CDA) of type I. Most of these mutations change the amino acids in codanina-1 protein, reducing its function. However, it is thought that these mutations do not completely eliminate the function of the protein, which appears to be essential for life. Although it is unclear how mutations cause the characteristic features of the disease somehow shortage codanina-1 functional alters the normal development of red blood cells.

The SEC23B gene, located on the short arm of chromosome 20 (20p11.23), encodes a component of a large group of proteins that interact calls layer II protein complex (COPII). COPII is involved in the formation of vesicles that transport proteins and other materials into cells. More specifically, COPII vesicle formation triggers in the endoplasmic reticulum (ER), which is involved in the processing and transport of proteins. These COPII vesicle transport proteins intended to be secreted outside the cells. The protein encoded by the gene SEC23B is very similar to the protein encoded from SEC23A gene. These proteins are the two components of COPII, and they seem to have overlapping functions. In most cells, if one of these proteins is not found, the other may be able to compensate for the loss. However, SEC23B protein may have a unique role in developing erythroblasts.

They have identified at least 20 SEC23B gene mutations in people with congenital dyserythropoietic anemia (CDA) type II. Most of these mutations change the amino acid building blocks in the protein. Other mutations eliminate the gene or genetic material alter the way in which the gene encoding the protein. It is likely that mutations responsible for the disease type II disrupt the function of the protein, although not completely eliminated. It is unclear how mutations in the gene cause the characteristic features of type II disease. The abnormal protein leads to production of erythroblasts unusual shape may have additional cores. These defective erythroblasts can not become functional mature red blood cells. The decrease in healthy red blood cells leads to the signs and symptoms of anemia and complications, including hepatosplenomegaly and abnormal accumulation of iron that can damage organs in the body.

The inheritance pattern of Dyserythropoietic anemia depends on the type of disease. Types I and II are 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. Type III seems to have an autosomal dominant pattern of inheritance in several families. Autosomal dominant inheritance means that a copy of the altered gene in each cell is sufficient to cause the alteration. In these families, affected individuals often have a father and other relatives with the disease.  

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with congenital dyserythropoietic anemia, by complete PCR amplification of the exons of CDAN1 and SEC23B, respectively, and subsequent sequencing genes.

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).