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 42-year-old man has progressive sensorineural hearing
loss. Genetic testing reveals a frameshift mutation in a
gene required for cochlear hair-cell structure. Which
molecular consequence best explains how this frameshift
,causes a nonfunctional protein and the patient's
phenotype?
Options
A. A single amino-acid substitution in an extracellular
domain that mildly alters protein function
B. Creation of an early stop codon resulting in a truncated
polypeptide and nonsense-mediated decay
C. Expansion of a trinucleotide repeat that increases
protein expression
D. A synonymous codon change that reduces mRNA
stability
Correct Answer
B
Rationales
Correct: Frameshift mutations often produce aberrant
reading frames and premature stop codons; resulting
truncated proteins are unstable or degraded via nonsense-
mediated mRNA decay, causing loss of function.
A: A single amino-acid substitution is typical of missense
mutations and may not abolish protein function entirely.
C: Trinucleotide repeat expansions cause specific
syndromes (e.g., Huntington), but expansion typically
affects function by toxic gain or aggregation rather than
simple loss by truncation.
D: Synonymous changes do not change amino acids and
,rarely produce the severe loss-of-function seen with
frameshifts.
Teaching Point
Frameshifts → altered reading frame → premature stop
codon → truncated protein or mRNA decay.
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 cancer patient's tumor sequencing shows loss-of-
function mutations in a mismatch repair (MMR) gene.
Which downstream cellular consequence most directly
increases the tumor's mutational burden?
Options
A. Failure to repair single-strand base mismatches during
DNA replication
B. Increased chromosomal nondisjunction during mitosis
C. Reduced double-strand break repair by homologous
recombination
, D. Global hypermethylation of CpG islands leading to
silencing of tumor suppressors
Correct Answer
A
Rationales
Correct: MMR defects cause failure to correct base–base
mismatches and insertion/deletion loops generated during
replication, increasing point mutation frequency and
microsatellite instability.
B: Nondisjunction causes aneuploidy but is not the primary
effect of MMR loss.
C: Homologous recombination defects involve different
repair pathways (e.g., BRCA), not MMR.
D: Altered methylation affects gene expression but is an
epigenetic mechanism distinct from defective mismatch
repair.
Teaching Point
MMR deficiency → uncorrected replication errors → high
point mutation/microsatellite instability.
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 42-year-old man has progressive sensorineural hearing
loss. Genetic testing reveals a frameshift mutation in a
gene required for cochlear hair-cell structure. Which
molecular consequence best explains how this frameshift
,causes a nonfunctional protein and the patient's
phenotype?
Options
A. A single amino-acid substitution in an extracellular
domain that mildly alters protein function
B. Creation of an early stop codon resulting in a truncated
polypeptide and nonsense-mediated decay
C. Expansion of a trinucleotide repeat that increases
protein expression
D. A synonymous codon change that reduces mRNA
stability
Correct Answer
B
Rationales
Correct: Frameshift mutations often produce aberrant
reading frames and premature stop codons; resulting
truncated proteins are unstable or degraded via nonsense-
mediated mRNA decay, causing loss of function.
A: A single amino-acid substitution is typical of missense
mutations and may not abolish protein function entirely.
C: Trinucleotide repeat expansions cause specific
syndromes (e.g., Huntington), but expansion typically
affects function by toxic gain or aggregation rather than
simple loss by truncation.
D: Synonymous changes do not change amino acids and
,rarely produce the severe loss-of-function seen with
frameshifts.
Teaching Point
Frameshifts → altered reading frame → premature stop
codon → truncated protein or mRNA decay.
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 cancer patient's tumor sequencing shows loss-of-
function mutations in a mismatch repair (MMR) gene.
Which downstream cellular consequence most directly
increases the tumor's mutational burden?
Options
A. Failure to repair single-strand base mismatches during
DNA replication
B. Increased chromosomal nondisjunction during mitosis
C. Reduced double-strand break repair by homologous
recombination
, D. Global hypermethylation of CpG islands leading to
silencing of tumor suppressors
Correct Answer
A
Rationales
Correct: MMR defects cause failure to correct base–base
mismatches and insertion/deletion loops generated during
replication, increasing point mutation frequency and
microsatellite instability.
B: Nondisjunction causes aneuploidy but is not the primary
effect of MMR loss.
C: Homologous recombination defects involve different
repair pathways (e.g., BRCA), not MMR.
D: Altered methylation affects gene expression but is an
epigenetic mechanism distinct from defective mismatch
repair.
Teaching Point
MMR deficiency → uncorrected replication errors → high
point mutation/microsatellite instability.
Citation
Kumar et al. (2021). Robbins Basic Pathology (10th Ed.).
Ch. 1.
3
