Transcript Scenario (cont.)

Objectives
After this lesson, the student will be able to:
• Explain autosomal dominant inheritance using familial
hypercholesterolemia (FH) as an example;
• Discuss the issues associated with late-onset genetic
disorders;
• Explain how cholesterol levels can be reduced when
treating FH; and
• Explain the significance of the identification of the
fragile X syndrome.
Scenario
Paul is rushed into intensive care where a diagnosis of acute myocardial infarction (heart
attack) is made. His cholesterol level is 325 mg/dL, and for a man of his age and
lifestyle, it should be well under 200 mg/dL. 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 (cont.)
The 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 a coronary bypass at the age of 57. She is adopted and no
further information about her family is known.
Familial Hypercholesterolemia (FH)
• Cholesterol basics
– LDL: bad cholesterol
– HDL: good cholesterol
• Gene on chromosome
#19, makes body
unable to remove LDL
• Cholesterol levels
unregulated
– LDL builds up
• Potentially fatal
• Autosomal dominant
Paul: Heterozygous for familial hypercholesterolemia
Stacy: Healthy
FH
FH
Key
F = FH
f = normal
normal
normal
Paul’s condition stabilizes and long term dietary and drug treatment is planned.
Paul is depressed because he thought that his healthful 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.
Fragile X
• Defected gene
on X
chromosome
– Recessive Xlinked
• Protein absent
• Mental
retardation
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 agrees to be tested and is found to have
normal levels of lipids - fatty 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. Deborah refuses testing.
She has no faith in medical science and relies instead on “folk medicine 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 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 know 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…”