Robbins Basic Pathology
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1)
Reference — Ch. 1 — The Genome
Question Stem
A 28-year-old woman with progressive sensorineural hearing
loss has children with variable severity of the same disorder.
Which genomic feature best explains the variable expression
seen among her offspring?
Options
A. Autosomal dominant transmission with incomplete
penetrance
B. Heteroplasmy of mitochondrial DNA mutations
,C. X-linked recessive transmission with lyonization in daughters
D. Anticipation caused by trinucleotide repeat expansion
Correct Answer: B
Rationales
• B (Correct): Mitochondrial DNA mutations are maternally
inherited and often present with heteroplasmy (mixture of
mutant and normal mtDNA) that produces variable
severity among offspring.
• A: Incomplete penetrance can cause variable expression
but would not explain consistent maternal transmission to
all children.
• C: X-linked recessive disorders have different transmission
patterns (typically males more affected); lyonization
explains variability in females but not maternal-only
inheritance to both sexes.
• D: Anticipation explains progressive earlier onset across
generations for repeat expansion disorders, not the
variable severity among siblings from the same mother.
Teaching Point
Mitochondrial heteroplasmy causes variable disease
expression in maternally inherited disorders.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
,2)
Reference — Ch. 1 — Cellular Housekeeping
Question Stem
A patient receives a proteasome inhibitor for multiple myeloma.
Which cellular consequence most directly results from
proteasome inhibition and contributes to myeloma cell death?
Options
A. Increased lysosomal degradation of organelles
B. Accumulation of ubiquitinated proteins leading to ER stress
and apoptosis
C. Enhanced autophagic flux that clears misfolded proteins
D. Increased mitochondrial biogenesis to meet ATP demand
Correct Answer: B
Rationales
• B (Correct): Proteasome inhibition causes buildup of
ubiquitinated/misfolded proteins in the cytoplasm and ER,
inducing ER stress and apoptotic pathways—therapeutic in
myeloma.
• A: Lysosomal degradation is separate from proteasomal
degradation; proteasome inhibition does not increase
lysosomal breakdown.
• C: In some cases autophagy may be induced as
compensation but proteasome inhibition primarily causes
accumulation rather than enhanced clearance.
• D: Proteasome inhibition does not directly stimulate
mitochondrial biogenesis to resolve protein accumulation.
, Teaching Point
Proteasome inhibition → ubiquitinated protein
accumulation → ER stress → apoptosis.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
3)
Reference — Ch. 1 — Cellular Metabolism and Mitochondrial
Function
Question Stem
A 56-year-old man develops exercise intolerance and lactic
acidosis after a suspected defect in mitochondrial oxidative
phosphorylation. Which of the following best explains why
tissues with high energy demand are most affected?
Options
A. High-demand tissues rely primarily on anaerobic glycolysis at
baseline
B. Mitochondrial defects impair ATP generation via oxidative
phosphorylation, especially in high-ATP–requiring tissues
C. Mitochondrial DNA mutations are selectively expressed in
skeletal muscle only
D. Mitochondrial dysfunction increases peroxisomal β-
oxidation, depleting energy substrates
Correct Answer: B
Rationales
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1)
Reference — Ch. 1 — The Genome
Question Stem
A 28-year-old woman with progressive sensorineural hearing
loss has children with variable severity of the same disorder.
Which genomic feature best explains the variable expression
seen among her offspring?
Options
A. Autosomal dominant transmission with incomplete
penetrance
B. Heteroplasmy of mitochondrial DNA mutations
,C. X-linked recessive transmission with lyonization in daughters
D. Anticipation caused by trinucleotide repeat expansion
Correct Answer: B
Rationales
• B (Correct): Mitochondrial DNA mutations are maternally
inherited and often present with heteroplasmy (mixture of
mutant and normal mtDNA) that produces variable
severity among offspring.
• A: Incomplete penetrance can cause variable expression
but would not explain consistent maternal transmission to
all children.
• C: X-linked recessive disorders have different transmission
patterns (typically males more affected); lyonization
explains variability in females but not maternal-only
inheritance to both sexes.
• D: Anticipation explains progressive earlier onset across
generations for repeat expansion disorders, not the
variable severity among siblings from the same mother.
Teaching Point
Mitochondrial heteroplasmy causes variable disease
expression in maternally inherited disorders.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
,2)
Reference — Ch. 1 — Cellular Housekeeping
Question Stem
A patient receives a proteasome inhibitor for multiple myeloma.
Which cellular consequence most directly results from
proteasome inhibition and contributes to myeloma cell death?
Options
A. Increased lysosomal degradation of organelles
B. Accumulation of ubiquitinated proteins leading to ER stress
and apoptosis
C. Enhanced autophagic flux that clears misfolded proteins
D. Increased mitochondrial biogenesis to meet ATP demand
Correct Answer: B
Rationales
• B (Correct): Proteasome inhibition causes buildup of
ubiquitinated/misfolded proteins in the cytoplasm and ER,
inducing ER stress and apoptotic pathways—therapeutic in
myeloma.
• A: Lysosomal degradation is separate from proteasomal
degradation; proteasome inhibition does not increase
lysosomal breakdown.
• C: In some cases autophagy may be induced as
compensation but proteasome inhibition primarily causes
accumulation rather than enhanced clearance.
• D: Proteasome inhibition does not directly stimulate
mitochondrial biogenesis to resolve protein accumulation.
, Teaching Point
Proteasome inhibition → ubiquitinated protein
accumulation → ER stress → apoptosis.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
3)
Reference — Ch. 1 — Cellular Metabolism and Mitochondrial
Function
Question Stem
A 56-year-old man develops exercise intolerance and lactic
acidosis after a suspected defect in mitochondrial oxidative
phosphorylation. Which of the following best explains why
tissues with high energy demand are most affected?
Options
A. High-demand tissues rely primarily on anaerobic glycolysis at
baseline
B. Mitochondrial defects impair ATP generation via oxidative
phosphorylation, especially in high-ATP–requiring tissues
C. Mitochondrial DNA mutations are selectively expressed in
skeletal muscle only
D. Mitochondrial dysfunction increases peroxisomal β-
oxidation, depleting energy substrates
Correct Answer: B
Rationales
