Robbins & Cotran 10th Ed. Pathology Test Bank | Chapter-
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter Reference – The Cell as a Unit of Health and Disease /
The Genome
Stem: A newborn has severe combined immunodeficiency
(SCID) due to absent adenosine deaminase (ADA). Which
genomic defect best explains accumulation of toxic metabolites
that kill lymphocytes?
A. Missense mutation in a structural protein
B. Nonsense mutation causing early stop codon in ADA gene
C. Frameshift in a noncoding intron
D. Silent mutation in ADA exon leading to same amino acid
Answer: B
,Rationales:
• Correct (B): A nonsense mutation creates a premature stop
codon producing truncated or absent functional ADA
enzyme, causing toxic purine metabolite accumulation that
kills lymphocytes. This directly explains ADA-deficient SCID
pathogenesis.
• A: Missense mutations alter amino acids but may preserve
partial function; SCID from ADA typically results from loss-
of-function mutations like nonsense or frameshift.
• C: A frameshift in a noncoding intron is unlikely to alter
ADA protein because intronic sequences are spliced out.
• D: A silent mutation does not change amino acid sequence
and usually preserves ADA function unless it affects
splicing, which is not stated.
Teaching Point: Nonsense mutations often cause loss-of-
function by producing truncated, nonfunctional proteins.
2
Chapter Reference – The Genome / DNA Repair
Stem: A patient with xeroderma pigmentosum (extreme UV
sensitivity) has defective nucleotide excision repair. Which
lesion fails to be repaired, leading to skin cancer risk?
A. Double-strand DNA breaks from ionizing radiation
B. Thymine dimers induced by ultraviolet light
,C. Mismatch pairs from replication errors
D. Uracil incorporated into DNA
Answer: B
Rationales:
• Correct (B): UV light produces thymine (pyrimidine) dimers
that are removed by nucleotide excision repair; defective
repair causes mutation buildup and high skin cancer risk.
• A: Double-strand breaks are primarily repaired by
homologous recombination or nonhomologous end
joining, not nucleotide excision repair.
• C: Mismatch repair corrects replication errors; mismatch
defects cause Lynch syndrome, not xeroderma
pigmentosum.
• D: Uracil in DNA is removed by base excision repair; this
lesion is unrelated to UV-induced thymine dimers.
Teaching Point: Nucleotide excision repair removes UV-induced
pyrimidine dimers to prevent mutagenesis.
3
Chapter Reference – Cellular Housekeeping / Autophagy &
Lysosomes
Stem: A neuron shows accumulation of autofluorescent
lipofuscin with aging. This material most likely results from
impaired:
, A. Proteasomal degradation of ubiquitinated proteins
B. Autophagic digestion of damaged organelles in lysosomes
C. Endoplasmic reticulum–associated degradation (ERAD) only
D. Nuclear DNA repair
Answer: B
Rationales:
• Correct (B): Lipofuscin is undegraded residual material
from autophagy/lysosomal digestion of cellular debris;
accumulation reflects decreased autophagic-lysosomal
clearance with age.
• A: Proteasomes degrade short-lived or misfolded proteins,
not large organelles; lipofuscin specifically relates to
autophagic-lysosomal flux.
• C: ERAD handles misfolded proteins from the ER; it does
not account for lysosomal residual bodies like lipofuscin.
• D: Nuclear DNA repair does not generate lipofuscin; this
option is unrelated.
Teaching Point: Impaired autophagy/lysosomal function causes
accumulation of lipofuscin in long-lived cells.
4
Chapter Reference – Cellular Housekeeping / Ubiquitin-
Proteasome System
Stem: A cancer therapy inhibits the 26S proteasome. Which
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter Reference – The Cell as a Unit of Health and Disease /
The Genome
Stem: A newborn has severe combined immunodeficiency
(SCID) due to absent adenosine deaminase (ADA). Which
genomic defect best explains accumulation of toxic metabolites
that kill lymphocytes?
A. Missense mutation in a structural protein
B. Nonsense mutation causing early stop codon in ADA gene
C. Frameshift in a noncoding intron
D. Silent mutation in ADA exon leading to same amino acid
Answer: B
,Rationales:
• Correct (B): A nonsense mutation creates a premature stop
codon producing truncated or absent functional ADA
enzyme, causing toxic purine metabolite accumulation that
kills lymphocytes. This directly explains ADA-deficient SCID
pathogenesis.
• A: Missense mutations alter amino acids but may preserve
partial function; SCID from ADA typically results from loss-
of-function mutations like nonsense or frameshift.
• C: A frameshift in a noncoding intron is unlikely to alter
ADA protein because intronic sequences are spliced out.
• D: A silent mutation does not change amino acid sequence
and usually preserves ADA function unless it affects
splicing, which is not stated.
Teaching Point: Nonsense mutations often cause loss-of-
function by producing truncated, nonfunctional proteins.
2
Chapter Reference – The Genome / DNA Repair
Stem: A patient with xeroderma pigmentosum (extreme UV
sensitivity) has defective nucleotide excision repair. Which
lesion fails to be repaired, leading to skin cancer risk?
A. Double-strand DNA breaks from ionizing radiation
B. Thymine dimers induced by ultraviolet light
,C. Mismatch pairs from replication errors
D. Uracil incorporated into DNA
Answer: B
Rationales:
• Correct (B): UV light produces thymine (pyrimidine) dimers
that are removed by nucleotide excision repair; defective
repair causes mutation buildup and high skin cancer risk.
• A: Double-strand breaks are primarily repaired by
homologous recombination or nonhomologous end
joining, not nucleotide excision repair.
• C: Mismatch repair corrects replication errors; mismatch
defects cause Lynch syndrome, not xeroderma
pigmentosum.
• D: Uracil in DNA is removed by base excision repair; this
lesion is unrelated to UV-induced thymine dimers.
Teaching Point: Nucleotide excision repair removes UV-induced
pyrimidine dimers to prevent mutagenesis.
3
Chapter Reference – Cellular Housekeeping / Autophagy &
Lysosomes
Stem: A neuron shows accumulation of autofluorescent
lipofuscin with aging. This material most likely results from
impaired:
, A. Proteasomal degradation of ubiquitinated proteins
B. Autophagic digestion of damaged organelles in lysosomes
C. Endoplasmic reticulum–associated degradation (ERAD) only
D. Nuclear DNA repair
Answer: B
Rationales:
• Correct (B): Lipofuscin is undegraded residual material
from autophagy/lysosomal digestion of cellular debris;
accumulation reflects decreased autophagic-lysosomal
clearance with age.
• A: Proteasomes degrade short-lived or misfolded proteins,
not large organelles; lipofuscin specifically relates to
autophagic-lysosomal flux.
• C: ERAD handles misfolded proteins from the ER; it does
not account for lysosomal residual bodies like lipofuscin.
• D: Nuclear DNA repair does not generate lipofuscin; this
option is unrelated.
Teaching Point: Impaired autophagy/lysosomal function causes
accumulation of lipofuscin in long-lived cells.
4
Chapter Reference – Cellular Housekeeping / Ubiquitin-
Proteasome System
Stem: A cancer therapy inhibits the 26S proteasome. Which
