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 pregnant patient undergoes noninvasive prenatal
screening that identifies a high risk for a trinucleotide repeat
expansion disorder. Which molecular mechanism best explains
how an expanded repeated sequence can cause disease
expression in the fetus?
Options
A. Loss of function due to frameshift mutations in coding exons
B. Toxic gain-of-function via abnormal RNA or protein products
from expanded repeats
,C. Haploinsufficiency from single-allele promoter methylation
D. Increased chromosomal translocations leading to gene fusion
proteins
Correct Answer
B
Rationales
Correct (B): Expanded trinucleotide repeats frequently cause
disease by producing abnormal RNA or protein products (toxic
gain-of-function) that interfere with cell processes.
A: Frameshifts are caused by indels, not by repeat expansions
per se; repeat expansions often preserve reading frame.
C: Promoter methylation causing haploinsufficiency can cause
disease but is not the defining mechanism of trinucleotide
repeat disorders.
D: Chromosomal translocations and fusion proteins are
different mutational events not typical of repeat expansions.
Teaching Point
Trinucleotide expansions often produce toxic RNA/protein gain-
of-function.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — The Genome
,Question Stem
A hospitalized patient receives chemotherapy that causes DNA
crosslinking. Which genomic repair pathway, when deficient,
would most likely increase sensitivity to this agent and lead to
accumulation of double-strand breaks?
Options
A. Base excision repair
B. Nucleotide excision repair
C. Homologous recombination repair
D. Mismatch repair
Correct Answer
C
Rationales
Correct (C): Homologous recombination repairs double-strand
breaks accurately by using a sister chromatid; its deficiency
increases sensitivity to agents causing crosslinks and breaks.
A: Base excision repair fixes small base lesions, not double-
strand breaks primarily.
B: Nucleotide excision repair removes bulky adducts but is not
the primary double-strand break pathway.
D: Mismatch repair corrects replication errors; it does not
directly repair double-strand breaks.
Teaching Point
Homologous recombination repairs DNA double-strand breaks
using a sister chromatid.
, Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference
Ch. 1 — Cellular Housekeeping
Question Stem
A patient with progressive neurodegeneration shows
accumulation of ubiquitinated protein aggregates in neurons on
biopsy. Which disrupted cellular house-keeping pathway best
explains the accumulation?
Options
A. Autophagy–lysosomal degradation failure
B. Increased proteasomal activity clearing misfolded proteins
C. Enhanced chaperone-mediated refolding of proteins
D. Increased exocytosis of aggregated proteins
Correct Answer
A
Rationales
Correct (A): Failure of autophagy–lysosomal pathways impairs
clearance of large protein aggregates and damaged organelles,
promoting accumulation.
B: Increased proteasomal activity would decrease aggregates,
not cause accumulation.
C: Enhanced chaperone activity would favor refolding and
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 pregnant patient undergoes noninvasive prenatal
screening that identifies a high risk for a trinucleotide repeat
expansion disorder. Which molecular mechanism best explains
how an expanded repeated sequence can cause disease
expression in the fetus?
Options
A. Loss of function due to frameshift mutations in coding exons
B. Toxic gain-of-function via abnormal RNA or protein products
from expanded repeats
,C. Haploinsufficiency from single-allele promoter methylation
D. Increased chromosomal translocations leading to gene fusion
proteins
Correct Answer
B
Rationales
Correct (B): Expanded trinucleotide repeats frequently cause
disease by producing abnormal RNA or protein products (toxic
gain-of-function) that interfere with cell processes.
A: Frameshifts are caused by indels, not by repeat expansions
per se; repeat expansions often preserve reading frame.
C: Promoter methylation causing haploinsufficiency can cause
disease but is not the defining mechanism of trinucleotide
repeat disorders.
D: Chromosomal translocations and fusion proteins are
different mutational events not typical of repeat expansions.
Teaching Point
Trinucleotide expansions often produce toxic RNA/protein gain-
of-function.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
2
Reference
Ch. 1 — The Genome
,Question Stem
A hospitalized patient receives chemotherapy that causes DNA
crosslinking. Which genomic repair pathway, when deficient,
would most likely increase sensitivity to this agent and lead to
accumulation of double-strand breaks?
Options
A. Base excision repair
B. Nucleotide excision repair
C. Homologous recombination repair
D. Mismatch repair
Correct Answer
C
Rationales
Correct (C): Homologous recombination repairs double-strand
breaks accurately by using a sister chromatid; its deficiency
increases sensitivity to agents causing crosslinks and breaks.
A: Base excision repair fixes small base lesions, not double-
strand breaks primarily.
B: Nucleotide excision repair removes bulky adducts but is not
the primary double-strand break pathway.
D: Mismatch repair corrects replication errors; it does not
directly repair double-strand breaks.
Teaching Point
Homologous recombination repairs DNA double-strand breaks
using a sister chromatid.
, Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.). Ch. 1.
3
Reference
Ch. 1 — Cellular Housekeeping
Question Stem
A patient with progressive neurodegeneration shows
accumulation of ubiquitinated protein aggregates in neurons on
biopsy. Which disrupted cellular house-keeping pathway best
explains the accumulation?
Options
A. Autophagy–lysosomal degradation failure
B. Increased proteasomal activity clearing misfolded proteins
C. Enhanced chaperone-mediated refolding of proteins
D. Increased exocytosis of aggregated proteins
Correct Answer
A
Rationales
Correct (A): Failure of autophagy–lysosomal pathways impairs
clearance of large protein aggregates and damaged organelles,
promoting accumulation.
B: Increased proteasomal activity would decrease aggregates,
not cause accumulation.
C: Enhanced chaperone activity would favor refolding and
