Clinical Cases Discussion- INTRODUCTION TO GENETICS WORKSHOP - Science Assignment Help

Week 3

Clinical Cases Discussion

Purpose: The clinical cases provided below are intended to expand the depth of content and your understanding of the Teaching Learning Objectives and develop your exposure to clinical language, thinking and reasoning. You are expected to use the learning modules, prescribed reading and your own research to review the cases outlined below. You are also expected to attend the live clinical case discussion sessions and actively participate. You should identify the meaning of any clinical terms and although clinical terminology is not assessable in General Principle it essential to begin building your clinical immersion as part of this introductory course. Additional reading is provided for your reference for some of the questions in the give case studies.

Case 1 – Phenylketonuria (PKU)

A couple presents to your practice for prenatal genetic testing and counseling. They already have two children. In taking a detailed history, you find out that one of their children is afflicted with a disease associated with enzymatic deficiency in metabolism of the amino acid phenylalanine (PKU). After obtaining further history from them and their family members, you drew the pedigree chart shown below. Using the pedigree provided, answer the following questions.

1. What is the most likely pattern of inheritance? Justify your answer and explain how it is different from other patterns of inheritance.

2. The couple are planning to have a third child. As one of their children is affected by the disease, they wanted to know the risk for their third child to have that particular disease and the probability of their phenotypically normal child carrying the disease allele. What advice would you give to the couple?

3. Is there any genetic testing available to screen the fetus /newborn for PKU? Why is it important to do newborn screening/ test for the presence of this disease (what are the implications)?

4. If the prevalence of PKU is 1/10000 live births, calculate disease allele frequency and carrier frequency in the population using the Hardy-Weinberg equation. What is the proportion of matings in this population that could produce an affected child (i.e., the probability that 2 carriers (heterozygous individuals) will mate)?

Case 2 - Down Syndrome

A 45-year-old female is pregnant for the first time. As this is a very desired pregnancy, she wants to know any risks to the fetus due to her advanced maternal age. The GP explains that the risk of chromosomal abnormalities is increased due to advanced maternal age and refers her for chorionic villus sampling and testing of the fetal genome. The following karyotyping is obtained from the fetal chromosomal analysis. Use this karyotyping to answer the following questions.

1. What is the abnormality that you see in this karyotyping?

2. Explain the most common cause for this abnormality and describe nondisjunction of the chromosome.

3. List the main clinical features related to this particular condition.

Case 3 – Hemophilia

A 38-year-old woman in good health, made an appointment for genetic counseling to discuss her risk of having a child with hemophilia. She had a maternal uncle who died from hemophilia during childhood, and her brother experienced bleeding issues as a child but improved as he grew older. No other family members had any bleeding disorders. The geneticist explained to her that her family history indicated a potential X-linked abnormality in blood clotting, such as hemophilia A or B. The fact that her brother's condition improved strongly suggested a diagnosis of the hemophilia B variant called factor IX Leyden. In order to confirm this diagnosis, the geneticist asked to evaluate her brother first, as it can be challenging to identify isolated carriers. The brother’s medical records revealed that he had been diagnosed with factor IX deficiency as a child but now had almost normal levels of factor IX in his blood. DNA mutation analysis confirmed that he carried a mutation in the F9 gene promoter, which matches factor IX Leyden. Further testing showed that she did not carry the same mutation as her brother.

1. What is hemophilia? List different types of hemophilia and the genetic basis of the disease.

1. What are the common clinical presentations of hemophilia? Outline the treatment modalities.

1. How do you explain the improvement in her brother’s condition (now had almost normal levels of factor IX in his blood)?

1. The figure below shows the family pedigree of the patient. If testing showed that the patient (III – 2) is a carrier for the mutation in F9. What is the risk that her son (the male in generation IV) is affected with hemophilia? What is the risk that her daughter is a heterozygous carrier? What is the risk that she (the daughter) is affected by the disorder?

1. The prevalence of hemophilia B in the population is 1:40000 males. What are the gene frequency and the heterozygote frequency for each of these?

Case 4 - Alzheimer disease

An elderly woman with dementia, experienced a decline in her short-term memory that was noticed by her family eight years before her death. Initially, they attributed it to typical forgetfulness associated with old age. However, her cognitive decline continued and started to interfere with her ability to drive, shop, and take care of herself. Medical evaluations ruled out conditions such as thyroid disease, vitamin deficiency, brain tumor, drug intoxication, chronic infection, depression, or strokes. Magnetic resonance imaging (MRI) of her brain revealed widespread cortical atrophy. She had a family history of dementia, with her brother, father, and two other paternal relatives dying from the condition in their 70s. A neurologist explained to the patient and her family that significant declines in memory and judgment are not a normal part of aging. Given her cognitive decline, behavioral disturbances, and impaired daily functioning, the neurologist suspected a clinical diagnosis of dementia, potentially late onset Alzheimer's disease. This suspicion was further supported by her apolipoprotein E genotype: APOE ?4/?4. Over the next year, her condition deteriorated rapidly, and she passed away in hospice care at the age of 82. The autopsy confirmed the diagnosis of Alzheimer's disease.

1. What is the mode of inheritance of Alzheimer’s disease?

1. What environmental factors are proposed for the remaining risk? What are the difficulties with conclusively identifying environmental factors as risks?

1.  List factors increasing the recurrence risk in the offspring.

1. Discuss the genetic abnormalities associated with both late onset and early onset AD.