CPR 8.02 Genetics of Cardiomyopathy

Question 1

What is the most common mode of inheritance of FHC and DCM

Answer 1

Autosomal Dominant

Question 2

What are the basic pathologic findings in FHC?

Answer 2

LVH, sarcomere hypertrophy, myocardial disarray. Moderation in ALL physical activities.

Question 3

What are the basic pathologic findings in DCM?

Answer 3

Enlargement of left ventricle and atrium with impaired systolic contractile function.

Question 4

Identify the four genes responsible for ~90% of FHC. And the function of the prtoein coded for by each of these genes

Answer 4

A. MYH7: Cardiac B-Myosin heavy chain 7, essential protein of the thick filament.
B. MYBPC3: Myosin binding protein C, Cardiac type, holds the thick filament together like a rubber band.
C. TNNT2: Cardiac troponin T, regulation of Ca++ mediated actin/myosin association.
D. TNNI3: Cardiac troponin I, regulation of Ca++ mediated actin/myosin association.

Question 5

Identify the two genes responsible for ~25% of DCM. And the function of the protein coded for by each of these genes.

Answer 5

A. TTN: Titin protein. Largest known protein, spans from Z disc to M line and functions like a spring to keep myosin filaments centered in the sarcomere.
B. LMNA: Nuclear lamin-A/C: support structure for the nucleus.

Question 6

Contrast the common phenotype in individuals with MYH7 mutations and MYBPC3 mutations.

Answer 6

1. MYH7: Onset in 2nd decade of life.

2. MYBPC3: Onset in 4th-5th decade of life.

Question 7

What type of mutations most commonly cause FHC and what does this suggest about the pathophysiolgy?

Answer 7

Most FHC mutations are missense mutations: suggests the disease is a result of incorporation of improperly formed proteins into the sarcomere.

Question 8

Predict the clinical presentation of a patient with a MYBPC3 missense mutation

Answer 8

MYBC3 missense mutations more commonly seen in childhood: Misfolded protein Was incorporated into sarcomere.

Question 9

Predict the the clinical presentation of a patient with a MYBPC3 frameshift mutation

Answer 9

B. MYBC3 frameshift mutations more commonly seen in adult-onset cases. There won’t be a misflded protein added (functioning wall but half the size), eventually this catches up to you.

Question 10

What is a common progression of Sx in FHC? Though realize it doesn’t necessarily follow linearly.

Answer 10

CP, SOB, Palp’s, A/V Arrhythmias, HF, Sudden death.

Question 11

What are common Sx of DCM?

Answer 11

Heart failrue with sympetoms of congestion, arrhythmias, thromboembolic disease.