ScenarioPaul 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…?”

Scenario continuedThe genetics staff explains that 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. 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.

Familial Hypercholesterolemia (FH)• Cholesterol

levels unregulated– Builds up

• Gene on chromosome #19

• Potentially fatal

• Autosomal dominant

Key

F = FH disease

f = normal

FH FH

normal normal

Paul: Heterozygous for familial hypercholesterolemia

Stacy: Healthy

ScenarioPaul’s condition stabilizes and long term dietary and drug treatment is planned. Paul is depressed because he thought that his healthy lifestyle would have protected him against such an event. The genetics staff explains that his lifestyle may have actually postponed his heart attack or reduced its severity.

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.

ScenarioPaul 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.

Fragile X

• Defected gene on X chromosome– Recessive X-

linked

• Protein absent

• Mental retardation

Scenario continuedPaul 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 agrees to be tested and 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.

Scenario continuedDeborah refuses testing. She has no faith in medical science and relies instead on “folk medicines and certain helpful visions”. 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. She believes that if her life is shortened by heart disease, she will be “reincarnated as a Galapagos turtle or something else that lives a long time, because y’know, everything balances out. My brother Johnnie, he had a rough life but I bet now he’s a lion or a dolphin or something great like that.” Plans are made to test

Stacy’s children. “Go ahead and test Michelle and Alan. I don’t think that you need to test Frank.” The genetics staff reviewed the basics of autosomal dominant inheritance. “I understand that. It’s just that…well…there’s a good chance that Paul isn’t Frank’s father…”

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.

Key

H = Huntington’s disease

h = healthy

disease disease

disease healthy

?

Marcus Betty

Hh Hh