Purpose: topic Beta Thalaassemia
For the “Genetics A to Z†project, each student is assigned a genetic disorder to research-based upon his or her last name and assigned by your section faculty. A spreadsheet with each student’s name and assigned disorder can be found posted at the bottom of this section. The main goal of this project is to expose students to the resources available for genetics research. Additionally, students will gain knowledge about a disease and the possibilities for treatment.
Beta Thalaassemia is the topic for this research
Resources:
Students should begin by looking at the OMIM database, found at https://www.ncbi.nlm.nih.gov/omim Review the resources given to you by Dr. Whitt in Unit 1. The GWUMC Genetics website, www.gwumc.edu/edu/obgyn/genetics, is also a beneficial resource. Any of the genetics textbooks listed for this course may be helpful. Make sure your references are high quality and from authoritative sources, such as peer reviewed journal articles.
Format:
Each student is responsible for a word document written in APA format, double spaced, 12 point font, with title and reference page that will include the following headings and information: (note: an abstract is not required)
Name(s) of disease
Inheritance pattern and family history
Chromosomal location of gene(s) and mutation(s)
OMIM number (if available)
Incidence in population (include ethnic/racial/geographic prevalence if known)
Explanation of gene(s) (What is the normal gene function) and type of mutation(s) involved (e.g. gain of function, TSG)
Pathophysiology of the disease (How do the gene(s) or mutation(s) contribute to disease)
Diagnosis-genotype/phenotype (Include genetic testing if available and other laboratory and diagnostic testing)
Treatment (include gene therapy, enzyme replacement, medications etc.)
Support groups and web sites for these
Long-term outcome if known
Writing:
Writing should be at a graduate level with well-constructed sentences and paragraphs, following correct rules for grammar and spelling. Students should paraphrase sources in their own words. The use of direct quotes should be minimal and less than 5% of the paper.
Submitting Assignment:
After completing the assignment, students should upload their assignment in Word format to the grade center through the assignment link found in the assignment section.
Optional: If you would like to share your work with your classmates, please go to the discussion board \”Optional Genetics A to Z\” forum and create a thread with your name and the name of the genetic condition you researched and upload a link to your paper. This is optional, but is a fun and interesting way to share your work so others can learn about all the different genetic conditions.
Grading Rubric: Genetics A-Z Assignment
Key: 0=Incomplete 1=Poor 2= Fair 3= Good 4=Excellent
0
1
2
3
4
Name of disease stated
Inheritance pattern and family history explained
Chromosomal location of gene mutation identified and stated correctly
OMIM number stated (if available)
Incidence in the population explained (Including incidence in general population and racial/ethnic groups)
Genes and mutation(s) listed & explained
Pathophysiology of the disease and genetic mechanisms explained clearly
Diagnosis- genotype/ phenotype explained, Laboratory and Genetic tests if available explained clearly
Treatment explained clearly (if any, including gene therapy, enzyme replacement, medications etc.)
Support groups and websites for these included
Long-term outcomes explained if known
APA format
Neatness and clarity
Writing quality
Grammar and spelling
16. Reference quality (authoritative sources)
Beta-thalassemia
Student’s Name
Institutional Affiliations
Beta-thalassemia
Name of Disease
Beta-thalassemia is a blood disorder characterized by an impairment in the production of functional hemoglobin. This inherited disease usually causes a condition known as chronic hemolytic anemia as it deprives the body tissues of oxygen (National Organization of Rare Diseases, 2021). Beta-thalassemia usually occurs in three forms namely; minor thalassemia, intermedia thalassemia, and major thalassemia based on severity. Beta-thalassemia minor is a mild form of the disease. The disease is normally asymptomatic at this stage and individuals are beta-thalassemia carriers. Individuals with beta-thalassemia intermedia usually present with moderately severe symptoms while major thalassemia, also known as Cooley’s anemia is usually characterized by severe anemia (Zhong et al., 2018).
Inheritance Pattern and Family History
The inheritance pattern of beta-thalassemia occurs in an autosomal recessive manner. This explains why beta-thalassemia is classified as an autosomal recessive disorder. Basically, the hemoglobin beta (HBB) gene in each cell must have mutations associated with the disease for the condition to be inherited from parents to offspring. For parents to give birth to a child with beta-thalassemia, each one of them must carry a copy of the mutated HBB gene. Therefore, a family history of beta-thalassemia increased a person’s risk of developing the disease especially when both parents are carriers (Genetic and Rare Diseases Information Center (GARD), n.d.). This inheritance pattern is common with beta-thalassemia major and intermedia.
Chromosomal Location of Gene and Mutation
Gene mutation in beta-thalassemia occurs on the HBB gene. It may also occur on chromosome 11p15.4. The type of mutation on the HBB gene as well as on chromosome 11p15.4 can be either homozygous or compound heterozygous mutation. Apart from a gene mutation, beta-thalassemia may also be attributed to a deletion of the whole HBB gene cluster or of sequences 5-prime from the HBB gene cluster. Disease occurrence due to gene mutation and deletion are abbreviated as HBB; 141900 and LCRB; 152424 respectively (OMIM.org).
OMIM Number
The OMIM number for beta-thalassemia is # 613985. The (#) sign has been included in the OMIM number because the type of HBB gene mutation associated with beta-thalassemia can be homozygous or compound heterozygous mutation (OMIM.org).
Incidence in Population
Beta-thalassemia rarely occurs in the United States. However, the estimated incidence rate of minor thalassemia worldwide is 1 in 100,000 individuals. High prevalence rates of thalassemia are normally recorded among people and families from the Mediterranean, Middle East, Africa, Central Asia, the Indian subcontinent, and the Far East (National Organization of Rare Diseases, 2021; Zhong et al., 2018).
Explanation of Gene
Normal HBB gene function results in the sufficient production of beta globin-chains required for the synthesis of hemoglobin A. HBB gene function is impaired when there is a mutation in the gene. The two types of mutations that can occur in beta-thalassemia are that on the HBB gene or another one on chromosome 11p15.4. Following this mutation, gene function is affected leading to an imbalance in the production of beta-globin chains relative to alpha-globin chains (OMIM.org).
Pathophysiology of the Disease
The pathophysiology of beta-thalassemia involves chaperone HSP70. In normal human hemoglobin, normal erythroblasts are produced leading to the expression of chaperone HSP70. At later stages of maturation of these erythroblasts, chaperone HSP70 translocates into the nucleus to facilitate GATA1 protection from CASP3 cleavage. The chaperone primarily plays a role in the refolding of proteins that have undergone denaturation. In the process, it prevents these proteins from aggregation. In beta-thalassemia, there is an imbalance in the production of beta-globin chains relative to alpha-globin chains. During erythroblast maturation, the alpha-globin chains interact with chaperone HSP70. The chaperone is sequestered in the process thereby limiting its ability to protect GATA1 and cell apoptosis occurs (OMIM.org).
Diagnosis
The diagnosis of beta-thalassemia is based on symptom identification, clinical evaluation, and specialized tests. Symptoms of beta-thalassemia major include; a swollen abdomen, failure to thrive, and anemia symptoms such as extreme fatigue. These usually occur in childhood in the first two years of life. Besides, newborn screening is usually conducted to detect the hemoglobin disorder. Blood tests such as a complete blood count (CBC) and hemoglobin electrophoresis can tell changes or variations in blood hemoglobin concentration. Beta-thalassemia can also be detected using molecular genetic testing. Other tests such as amniocentesis or chorionic villus sampling (CVS) have successfully been used in prenatal diagnosis (National Organization of Rare Diseases, 2021).
Treatment
Treatment interventions for beta-thalassemia are usually chosen based on disease severity. The recommended treatment option for individuals with beta-thalassemia minor is folic acid supplementation to boost red blood cells production. Patients with beta-thalassemia intermedia and major are usually treated with blood transfusion to address anemia (National Organization of Rare Diseases, 2021). However, since repeated blood transfusion causes iron overload, the United States Food and Drug Administration (FDA) recommends the use of medications or chelation therapy and folic acid to help lower the level of iron in the blood. The FDA-approved drug for use with folic acid is Reblozyl. In rare cases, surgical removal of the spleen is normally considered to help improve thalassemia symptoms (National Organization of Rare Diseases, 2021).
Support Groups, and Long-Term Outcome
Support groups that are required to enhance the achievement of long-term outcomes include physicians, nurses, physical therapists, social workers, and genetic counselors experienced in beta-thalassemia management. Family members are also important support systems in the lives of patients with beta-thalassemia. The long-term therapeutic outcome for patients with beta-thalassemia is an improvement in disease symptoms, particularly those that are related to anemia. However, it is important to note that since beta-thalassemia is a genetic disorder, patients require periodic lifelong treatment in order to achieve an improved quality of life.
References
Genetic and Rare Diseases Information Center (GARD). (n.d.). Beta-thalassemia. https://rarediseases.info.nih.gov/diseases/871/beta-thalassemia
National Organization of Rare Diseases. (2021). Beta-thalassemia. https://rarediseases.org/rare-diseases/thalassemia-major/
OMIM.org. # 613985: Beta-thalassemia. https://omim.org/entry/613985.
Zhong, L., Gan, X., Xu, L., Liang, C., Xie, Y., Lin, W., Chen, P. & Liu, M. (2018). The phenomena of balanced effect between α-globin gene and of β-globin gene. BMC Medical Genetics 19, 145. https://doi.org/10.1186/s12881-018-0659-9