Disorders of Unstable Repeat Sequences Flashcards
Which one of the following statements regarding instability of unstable repeat sequences is correct?
A.The instability may lead to an increase or a decrease in repeat length intergenerationally or somatically.
B.All unstable repeat disorders are autosomal dominant.
C.All unstable repeat disorders are caused by trinucleotide repeat expansion.
D.Expansion of unstable repeats are loss-of-function changes due to methylation
E.None of the above.
***A.The instability may lead to an increase or a decrease in repeat length intergenerationally or somatically.
Which one of the following disorders is NOT caused by the expansion of unstable repeat sequences?
A. Duchenne muscular dystrophy
B. Fragile X syndrome
C. Friedreich ataxia
D. Huntington disease
E.Myotonic dystrophy type 1
F.Myotonic dystrophy type 2
***A. Duchenne muscular dystrophy
Which one of the following disorders is NOT caused by the expansion of trinucleotide repeat sequences?
A. Fragile X syndrome
B. Friedreich ataxia
C. Huntington disease
D.Myotonic dystrophy type 1
E.Myotonic dystrophy type 2
F.All of the above
G.None of the above
***E.Myotonic dystrophy type 2
CCTG tetranucleotide repeat
Which one of the following disorders of unstable repeat expansion does NOT exhibit dominant inheritance patterns?
A. Fragile X syndrome
B. Friedreich ataxia
C. Huntington disease
D.Myotonic dystrophy type 1
E.Myotonic dystrophy type 2
F.All of the above
G.None of the above
***B. Friedreich ataxia
Which one of the following disorders of unstable repeat expansion has the repeat sequence in the coding region?
A. Fragile X syndrome
B. Friedreich ataxia
C. Huntington disease
D.Myotonic dystrophy type 1
E.Myotonic dystrophy type 2
F.All of the above
G.None of the above
***C. Huntington disease
6 yo boy with epilepsy and grandfather with Huntington. Testing of grandfather showed 44 repeat of CAG in HTT. The boy’s father is asymptomatic with 52 copies. Huntington test showed 25/66 CAG repeats in the boy. Which one of the following would be the most appropriate interpretation of the allelic difference between the grandfather, the father, and the boy?
A. Anticipation
B. Epistasis
C.Lab error with wrong specimens
D. PCR artifacts
E. Pleiotropy
F.None of the above
***A. Anticipation
Child with tremor and epilepsy. Chromosome microarray found a 300-kb interstitial deletion on 4p16.3 including the HTT gene. Trinucleotide repeats test for Huntington disease on the patient detected homozygous 25 CAG repeats. What would be the most appropriate interpretation of the chromosome microarray results?
A. Normal
B.Unknown clinical significance, likely benign
C. Unknown clinical significance
D.Unknown clinical significance, likely pathogenic
E. Pathogenic
***A. Normal
The doctor ordered trinucleotide repeats test for Huntington disease. The results showed that the patient had compound heterozygous 30/65 copies of CAG in the HTT gene. When a genetic counselor saw this family, she mentioned that the likelihood that the patient inherited the mutated copy from his biological father was:
A. 10%
B. 30%
C. 50%
D. 60%
E. 90%
*** E. 90%
In which part of the HTT gene is the trinucleotide unstable repeat for Huntington disease is located?
A. Promoter
B. 5′ UTR
C. Intron
D. Exon
E. 3′ UTR
***D. Exon
first exon
Which one of the following genetic alterations in the HTT gene causes Huntington disease?
A. Point mutations
B. in/del
C.(CAG)n repeats in an intron
D.(CAG)n repeats in an exon
E.(CGG)n repeat in an intron
F.(CGG)n repeat in an exon
G.(CTG)n repeat in an intron
H.(CTG)n repeat in an exon
***D.(CAG)n repeats in an exon
Which one of the following molecular genetic assays is the most appropriate for the diagnosis of Huntington disease in clinical laboratories?
A. Chromosome karyotype
B. Chromosome microarray (CMA)
C.Multiplex ligation-dependent probe amplification (MLPA)
D.PCR/capillary electrophoresis and Southern blot
E. PCR/capillary electrophoresis
F. Triplet repeat–primed PCR
***D.PCR/capillary electrophoresis and Southern blot
Prenatal counseling. The wife had 24/35 copies of CAG repeats in the HTT gene for Huntington disease (HD), which were not interrupted by CCG repeats. She was 32 years old and had no HD symptoms. Which one of the following would most likely be the risk of HD in her children?
A. 0.5%
B. 30%
C. 50%
D. 80%
E. 100%
***C. 50%
Prenatal testing. The husband has 24/35 copies of the CAG repeats in the HTT gene for Huntington disease (HD), which are not interrupted by the CCG repeats. He is 42 years old and has no HD symptoms. Which one of the following would most likely be the risk of HD in his children?
A. 0.5%
B. 10%
C. 50%
D. 80%
E. 100%
***C. 50%
The husband is 42 years old and has no symptoms of HD. A molecular test detects that he has 16/25 CAG repeats. What is the clinical significance of the results?
A.The husband may not develop Huntington disease.
B.The husband does not have Huntington disease. But his children will be at risk.
C.The husband may develop Huntington disease. His children have 10% to 50% chance of having HD.
D.The husband has Huntington disease. His children have 50% chance of having HD.
E.None of the above.
***E.None of the above.
The results showed that BJ has 20/38 copies of CAG in the HTT gene. What would be the interpretation of this result?
A.BJ had normal alleles.
B.BJ had a gray zone mutation.
C.BJ had a premutation.
D.BJ had a full mutation.
***D.BJ had a full mutation.
Molecular testing shows that he has 18/34 CAG repeats. What is the clinical significance of the results?
A.The husband does not have Huntington disease.
B.The husband does not have Huntington disease, but his children will be at risk.
C.The husband may develop Huntington disease, and his children have a 10%–50% chance of having HD.
D.The husband has Huntington disease, and his children have a 50% chance of having HD. E.None of the above.
***B.The husband does not have Huntington disease, but his children will be at risk.
Molecular testing shows that he has 19/38 CAG repeats. What is the clinical significance of the results?
A.The husband does not have Huntington disease.
B.The husband does not have Huntington disease, but his children will be at risk.
C.The husband may develop Huntington disease, and his children have a 10%–50% chance of having HD.
D.The husband has Huntington disease, and his children have a 50% chance of having HD. E.None of the above.
***D.The husband has Huntington disease, and his children have a 50% chance of having HD.
Molecular testing shows that he has 20/41 CAG repeats. What is the clinical significance of the results?
A.The husband does not have Huntington disease.
B.The husband does not have Huntington disease, but his children will be at risk.
C.The husband may develop Huntington disease, and his children have a 10%–50% chance of having HD.
D.The husband has Huntington disease, and his children have a 50% chance of having HD. E.None of the above.
***D.The husband has Huntington disease, and his children have a 50% chance of having HD.
Acknowledging the technical limitations of size analysis, the American College of Medical Genetics and Genomics (ACMG) supports which one of the following acceptable ranges for alleles with less than 50 repeats with Huntington disease clinical testing and as grading criteria for the College of American Pathology (CAP)/ACMG proficiency testing survey?
A.Consensus size ±1 repeats
B.Consensus size ±2 repeats
C.Consensus size ±3 repeats
D.Consensus size ±4 repeats
E.Consensus size ±5 repeats
***B.Consensus size ±2 repeats
Acknowledging the technical limitations of size analysis, the American College of Medical Genetics and Genomics (ACMG) supports which one of the following acceptable ranges for alleles with 50-70 repeats with Huntington disease clinical testing and as grading criteria for the College of American Pathology (CAP)/ACMG proficiency testing survey?
A.Consensus size ±1 repeats
B.Consensus size ±2 repeats
C.Consensus size ±3 repeats
D.Consensus size ±4 repeats
E.Consensus size ±5 repeats
***C.Consensus size ±3 repeats
Acknowledging the technical limitations of size analysis, the American College of Medical Genetics and Genomics (ACMG) supports which one of the following acceptable ranges for alleles with ?70 repeats with Huntington disease clinical testing and as grading criteria for the College of American Pathology (CAP)/ACMG proficiency testing survey?
A.Consensus size ±1 repeats
B.Consensus size ±2 repeats
C.Consensus size ±3 repeats
D.Consensus size ±4 repeats
E.Consensus size ±5 repeats
***D.Consensus size ±4 repeats
The pathogenesis of Huntington disease is:
A. Activating mutation
B. Loss of function
C.Novel property on the protein
D.Novel property on the RNA
E.Novel property on the DNA
F. Overexpression
***C.Novel property on the protein
Mom diagnosed at 52 with Huntington disease with compound heterozygous 17/38 repeats the (CAG)n. What would be the chance her son has the same condition?
A. 1/2
B. 1/4
C. 10%
D. Up to 1%
E. Not predictable
F.None of the above
***A. 1/2
