Case Study #1 You are an Army officer during the Korean War, and are in charge of a group of soldiers preparing to deploy from Fort Dix, New Jersey. In anticipation of deployment to an area endemic for Malaria, all of your soldiers were given the medication primaquine for antimalarial prophylaxis. Approximately 10% of black servicemen developed an acute but self-limited anemia due to hemolysis of red blood cells. A smaller number of white soldiers of Mediteranean origin developed a similar but more severe hemolytic anemia.

The basis for this drug- induced hemolytic anemia was found to be a genetically determined deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD). Case Study #1

Go to OMIM: Search the OMIM database for: G6PD Look up clinical synopsis, text, genetic defect and location of G6PD gene. Then try to answer the following questions: 1. Where is the G6PD gene located? 2. Why does deficiency of the G6PD gene lead to hemolytic anemia? 3. What is the hexose monophosphate shunt and how is it related to this disorder? 4. How would you test for this disorder in the population? Case Study #1

Case Study #2 A 27 year old man and his wife have been referred for the evaluation of infertility. When the couple was seen in the OBGYN clinic, a screening semen analysis demonstrated azospermia. The patient says that in general he is well except for a long history of increased frequency of Upper Respiratory Infections. Your recall reading about a variant of Cystic Fibrosis associated with respiratory symptoms and infertility.

Case Study #2 Go to OMIM: Search the OMIM database for: Cystic Fibrosis Look up clinical synopsis, text, genetic defect and location of the CF gene. Questions: 1.What is the most common mutation for CF? 2.Describe the molecular abnormality associated with CF? 3.Can you explain the occurrence of infertility in males with CF? 4.What is the specific genotype associated with infertility in males with CF?

Case Study #3 You are the on-call Genetic Councelor covering the Neonatal Intensive Case Unit. A baby delivered three days ago had a positive "Guthrie" test. This is a screening test for the detection of phenylketonuria (PKU), an inborn error of metabolism.

Case Study #3 Go to OMIM: Search the OMIM database for: Phenylketonuria (PKU). Look up clinical synopsis, text, genetic defect and treatment of PKU disease. Additional searching might give you information about the “Guthrie” Test. Questions: 1. Describe PKU, its incidence, mechanism of inheritance and treatment. 2. What is the “Guthrie Test? Who uses it and when? 3. As a genetic counselor, what do you tell the parents of this baby?

Familial, early-onset Alzheimer's disease About 5% of people with Alzheimer's disease have a strong family history of the disease, with several affected family members and an early age of onset (under the age of 60). Mutations in three different genes - the amyloid precursor protein (APP) gene, and the presenilin 1 and 2 (PS1 and PS2) genes - have been found in different families afflicted with early-onset familial Alzheimer's disease. The mutations are dominant, that is, the child of a sufferer has a 50% chance of inheriting the disease susceptibility. With the possible exception of PS2, mutations in these genes are highly penetrant, though the severity of the disease is variable. Together, mutations in the three genes account for about 20-50% of familial cases Case Study #4

Go to OMIM: Search the OMIM database for amyloid precursor protein. Look up the chromosome location, clinical synopsis, text, and genetic links to Alzheimer’s disease. Additional searching might give you information about Alzheimer’s disease and Down’s syndrome. Then, answer the following questions: 1. What is the chromosome location of APP? 2. What is the normal function of APP and what goes wrong in Alzherimer’s disease? 1. As a genetic councelor, what would you do with this information?

80% of heart disease patients have an inherited lipoprotein abnormality. Case Study #5