Robbins Basic Pathology
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A newborn is found to have recurrent infections and failure to
thrive. Genetic testing shows a frameshift mutation early in a
gene encoding a DNA repair enzyme. Which cellular
,consequence best explains the increased susceptibility to
infections?
Options
A. Increased apoptosis of lymphoid precursors due to
accumulation of unrepaired DNA damage
B. Global hypermethylation suppressing immune gene
expression
C. Enhanced mitochondrial ROS production causing neutrophil
dysfunction
D. Overactivation of autophagy reducing lymphocyte numbers
Correct Answer
A
Rationales
• A (correct): Frameshift mutations in DNA repair enzymes
lead to accumulation of DNA damage; rapidly dividing
lymphoid precursors are sensitive to unrepaired damage
and undergo apoptosis, reducing immune cell numbers
and function.
• B (incorrect): Hypermethylation is an epigenetic change
and is not the primary direct consequence of a frameshift
in a DNA repair enzyme.
• C (incorrect): Mitochondrial ROS may impair function but
is not the most direct link between defective DNA repair
and lymphoid depletion.
, • D (incorrect): Autophagy overactivation is not the
expected primary mechanism from loss of DNA repair
function.
Teaching Point
Defective DNA repair → DNA damage accumulation →
apoptosis of rapidly dividing cells.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A 45-year-old man with progressive ataxia is found to have
expanded trinucleotide repeats in a neuronal gene. Which
molecular mechanism best explains progressive worsening after
each generation in this family?
Options
A. Anticipation due to unstable repeat expansion during
gametogenesis
B. Increased somatic hypermutation in postmitotic neurons
over time
C. Progressive telomere shortening accelerating neuronal loss
D. Mitochondrial heteroplasmy increasing with maternal age
, Correct Answer
A
Rationales
• A (correct): Trinucleotide repeat disorders show
anticipation because unstable repeat expansions can
increase during gametogenesis, producing more severe
disease in successive generations.
• B (incorrect): Somatic hypermutation occurs in immune
cells, not as the primary cause of trinucleotide repeat
expansion.
• C (incorrect): Telomere shortening affects replicative
tissues and does not account for generational expansion.
• D (incorrect): Mitochondrial heteroplasmy is maternally
inherited and does not explain trinucleotide repeat
anticipation.
Teaching Point
Trinucleotide repeat expansion → genetic anticipation across
generations.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
10th Edition
Author(s)Vinay Kumar; Abul K. Abbas;
Jon C. Aster
TEST BANK
1
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A newborn is found to have recurrent infections and failure to
thrive. Genetic testing shows a frameshift mutation early in a
gene encoding a DNA repair enzyme. Which cellular
,consequence best explains the increased susceptibility to
infections?
Options
A. Increased apoptosis of lymphoid precursors due to
accumulation of unrepaired DNA damage
B. Global hypermethylation suppressing immune gene
expression
C. Enhanced mitochondrial ROS production causing neutrophil
dysfunction
D. Overactivation of autophagy reducing lymphocyte numbers
Correct Answer
A
Rationales
• A (correct): Frameshift mutations in DNA repair enzymes
lead to accumulation of DNA damage; rapidly dividing
lymphoid precursors are sensitive to unrepaired damage
and undergo apoptosis, reducing immune cell numbers
and function.
• B (incorrect): Hypermethylation is an epigenetic change
and is not the primary direct consequence of a frameshift
in a DNA repair enzyme.
• C (incorrect): Mitochondrial ROS may impair function but
is not the most direct link between defective DNA repair
and lymphoid depletion.
, • D (incorrect): Autophagy overactivation is not the
expected primary mechanism from loss of DNA repair
function.
Teaching Point
Defective DNA repair → DNA damage accumulation →
apoptosis of rapidly dividing cells.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — The Cell as a Unit of Health and Disease — The
Genome
Question Stem
A 45-year-old man with progressive ataxia is found to have
expanded trinucleotide repeats in a neuronal gene. Which
molecular mechanism best explains progressive worsening after
each generation in this family?
Options
A. Anticipation due to unstable repeat expansion during
gametogenesis
B. Increased somatic hypermutation in postmitotic neurons
over time
C. Progressive telomere shortening accelerating neuronal loss
D. Mitochondrial heteroplasmy increasing with maternal age
, Correct Answer
A
Rationales
• A (correct): Trinucleotide repeat disorders show
anticipation because unstable repeat expansions can
increase during gametogenesis, producing more severe
disease in successive generations.
• B (incorrect): Somatic hypermutation occurs in immune
cells, not as the primary cause of trinucleotide repeat
expansion.
• C (incorrect): Telomere shortening affects replicative
tissues and does not account for generational expansion.
• D (incorrect): Mitochondrial heteroplasmy is maternally
inherited and does not explain trinucleotide repeat
anticipation.
Teaching Point
Trinucleotide repeat expansion → genetic anticipation across
generations.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
