Scenario

2. Scenario Paul is rushed into intensive care where a diagnosis of acute myocardial infarction (heart attack) is made. His cholesterol level is 325mg%, and for a man of his age and lifestyle, it should be well under 200mg%. Stacy calls the genetics center because Paul’s cardiologist placed much emphasis on a review of Paul’s family history. He told Stacy that “Paul’s case looks like the type that runs in families. It amounts to an inherited tendency to early heart disease. By the way, how many children did you say you have…?”

3. Scenario continued Paul’s mother was revealed to have had a coronary bypass at the age of 57. She is adopted and no further information about her family is known. This type of familial hypercholesterolemia (FH) is determined by a single, autosomal dominant gene and that each of Paul’s children has a 50% chance of having inherited the gene.

4. Familial Hypercholesterolemia (FH) • Cholesterol levels unregulated • Builds up • Gene on chromosome #19 • Potentially fatal • Autosomal dominant

5. Paul: Heterozygous for familial hypercholesterolemia Stacy: Healthy f f F f F f F Key F = FH disease f = normal FH FH f f f f f normal normal

6. Scenario Paul’s condition stabilizes and long term dietary and drug treatment is planned. Plans are made to test other “at-risk” family members, in order to identify those who have inherited the gene and who could benefit from aggressive management. Look at it this way…your healthy lifestyle may have actually postponed the heart attack or reduced its severity. I exercise. I eat right. I thought my healthy lifestyle would have protected me from this. This is very depressing.

8. Scenario Paul had a younger brother, John, who died several years ago at the age of 18 in a car accident. He had fragile X syndrome, and was moderately retarded.

9. Scenario Paul had a younger brother, John, who died several years ago at the age of 18 in a car accident. He had fragile X syndrome, and was moderately retarded.

10. Fragile X • Defected gene on X chromosome • Recessive sex-linked • Protein absent • Mental retardation

11. Fragile X

12. Scenario continued Paul has a sister, Susan, who is 18 and another sister, Deborah, 19. Both are offered lipid testing to determine if either has inherited the gene for FH. Susan is found to have normal levels of lipids (fatty acid substances, including cholesterol) in the blood. Years ago, when John was diagnosed with Fragile X syndrome, she had her chromosomes tested to determine if she might carry a gene for Fragile X. The chromosome study had been normal. OK. I’ll have my lipids tested.

13. Scenario continued Deborah had been offered Fragile X chromosome testing when her brother was alive to see if she might be a carrier. She had refused Fragile X testing at that time as well. If my life is shortened by heart disease, I’m sure I’ll be reincarnated as a Galapagos turtle or something else that lives a long time, because y’know, everything balances out. No. I don’t want to be tested. Medical science is stupid and silly. I get all my questions answered by my medicines and visions. My brother Johnnie, he had a rough life but I bet now he’s a lion or a dolphin or something great like that.

14. Scenario continued Plans are made to test Stacy’s children. Are you sure? Remember the Punnett Square I showed you earlier? Every one of your children has a 50% chance of inheriting the gene for FH. Including Frank. Go ahead and test Michelle and Alan. I don’t think that you need to test Frank. I understand that. It’s just that…well…there’s a good chance that Paul isn’t Frank’s father…”

15. Random practice problem • Huntington’s disease is a dominant disorder found on chromosome 4. Betty and Marcus met at a support clinic they have been attending to help them cope with the knowledge of their illness with Huntington’s disease. They would like to know the risk of having a healthy child, now that Betty is pregnant. Hh Hh H h Marcus Betty H H H h Key H = Huntington’s disease h = healthy H disease disease ? H h h h h disease healthy