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 1 — The Genome
Question: Two adult monozygotic twins show different
susceptibilities to type 2 diabetes despite identical DNA
sequences. Which mechanism best explains their discordant
disease risk?
A. Point mutations (SNPs) acquired after birth
B. Copy-number variations inherited from parents
C. Epigenetic modifications affecting gene expression
D. Mitochondrial DNA heteroplasmy inherited paternally
Correct Answer: C
Rationale — Correct: Robbins describes how epigenetic
changes (DNA methylation, histone modification, noncoding
RNAs) alter gene expression without changing sequence,
causing phenotypic differences between genetically identical
,individuals.
Rationale — A: Somatic SNPs can occur, but widespread
phenotypic discordance in adults is more consistently explained
by epigenetics than newly acquired SNPs.
Rationale — B: CNVs are inherited structural variants and less
likely to explain discordance between monozygotic twins.
Rationale — D: Mitochondrial DNA is maternally inherited;
paternal transmission is not the usual explanation.
Teaching Point: Epigenetic regulation explains phenotypic
differences without DNA sequence changes.
Citation: Robbins & Cotran Pathologic Basis of Disease, 10th
Ed., Chapter 1 — The Genome. ClinicalKey+1
2) Chapter 1 — The Genome
Question: A patient presents with progressive external
ophthalmoplegia and muscle weakness. Genetic testing shows
a high proportion of mutant mitochondrial genomes in muscle
biopsy. Which inheritance pattern is most consistent with this
finding?
A. Autosomal dominant
B. Autosomal recessive
C. Maternal (mitochondrial) inheritance
D. X-linked recessive
Correct Answer: C
,Rationale — Correct: Robbins explains that mitochondrial DNA
is transmitted maternally and disorders due to mitochondrial
mutations display maternal inheritance and heteroplasmy.
Rationale — A: Autosomal dominant inheritance involves
nuclear genes, not mitochondrial genome heteroplasmy.
Rationale — B: Autosomal recessive requires biparental
inheritance of mutant alleles.
Rationale — D: X-linked recessive involves nuclear X-
chromosome genes, not mtDNA.
Teaching Point: Mitochondrial DNA disorders follow maternal
inheritance and heteroplasmy.
Citation: Robbins & Cotran Pathologic Basis of Disease, 10th
Ed., Chapter 1 — The Genome. ClinicalKey+1
3) Chapter 1 — Cellular Housekeeping
Question: A neurologic disorder is characterized by
accumulation of short-lived misfolded proteins in neuronal
cytoplasm. Which cellular system is primarily responsible for
degrading short-lived, ubiquitinated proteins?
A. Lysosomal autophagy
B. Ubiquitin–proteasome system
C. Endoplasmic reticulum–associated degradation (ERAD) only
D. Golgi-mediated proteolysis
Correct Answer: B
, Rationale — Correct: Robbins details that the ubiquitin–
proteasome pathway targets short-lived and abnormal proteins
for proteasomal degradation following ubiquitination.
Rationale — A: Autophagy handles long-lived proteins,
organelles, and bulk degradation, not mainly short-lived
ubiquitinated proteins.
Rationale — C: ERAD is a specialized pathway for misfolded
proteins in the ER but proteasome degrades ubiquitinated
cytosolic substrates broadly.
Rationale — D: The Golgi does not carry out primary
proteasomal degradation of ubiquitinated proteins.
Teaching Point: The ubiquitin–proteasome system clears short-
lived and misfolded cytosolic proteins.
Citation: Robbins & Cotran Pathologic Basis of Disease, 10th
Ed., Chapter 1 — Cellular Housekeeping. ClinicalKey+1
4) Chapter 1 — Cellular Housekeeping
Question: A child with a lysosomal storage disorder
accumulates glycosphingolipids within neurons. Which defect
most directly produces this intracellular accumulation?
A. Impaired proteasome activity
B. Deficient lysosomal hydrolase activity
C. Mitochondrial oxidative phosphorylation failure
D. Excessive autophagic flux
Correct Answer: B
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter 1 — The Genome
Question: Two adult monozygotic twins show different
susceptibilities to type 2 diabetes despite identical DNA
sequences. Which mechanism best explains their discordant
disease risk?
A. Point mutations (SNPs) acquired after birth
B. Copy-number variations inherited from parents
C. Epigenetic modifications affecting gene expression
D. Mitochondrial DNA heteroplasmy inherited paternally
Correct Answer: C
Rationale — Correct: Robbins describes how epigenetic
changes (DNA methylation, histone modification, noncoding
RNAs) alter gene expression without changing sequence,
causing phenotypic differences between genetically identical
,individuals.
Rationale — A: Somatic SNPs can occur, but widespread
phenotypic discordance in adults is more consistently explained
by epigenetics than newly acquired SNPs.
Rationale — B: CNVs are inherited structural variants and less
likely to explain discordance between monozygotic twins.
Rationale — D: Mitochondrial DNA is maternally inherited;
paternal transmission is not the usual explanation.
Teaching Point: Epigenetic regulation explains phenotypic
differences without DNA sequence changes.
Citation: Robbins & Cotran Pathologic Basis of Disease, 10th
Ed., Chapter 1 — The Genome. ClinicalKey+1
2) Chapter 1 — The Genome
Question: A patient presents with progressive external
ophthalmoplegia and muscle weakness. Genetic testing shows
a high proportion of mutant mitochondrial genomes in muscle
biopsy. Which inheritance pattern is most consistent with this
finding?
A. Autosomal dominant
B. Autosomal recessive
C. Maternal (mitochondrial) inheritance
D. X-linked recessive
Correct Answer: C
,Rationale — Correct: Robbins explains that mitochondrial DNA
is transmitted maternally and disorders due to mitochondrial
mutations display maternal inheritance and heteroplasmy.
Rationale — A: Autosomal dominant inheritance involves
nuclear genes, not mitochondrial genome heteroplasmy.
Rationale — B: Autosomal recessive requires biparental
inheritance of mutant alleles.
Rationale — D: X-linked recessive involves nuclear X-
chromosome genes, not mtDNA.
Teaching Point: Mitochondrial DNA disorders follow maternal
inheritance and heteroplasmy.
Citation: Robbins & Cotran Pathologic Basis of Disease, 10th
Ed., Chapter 1 — The Genome. ClinicalKey+1
3) Chapter 1 — Cellular Housekeeping
Question: A neurologic disorder is characterized by
accumulation of short-lived misfolded proteins in neuronal
cytoplasm. Which cellular system is primarily responsible for
degrading short-lived, ubiquitinated proteins?
A. Lysosomal autophagy
B. Ubiquitin–proteasome system
C. Endoplasmic reticulum–associated degradation (ERAD) only
D. Golgi-mediated proteolysis
Correct Answer: B
, Rationale — Correct: Robbins details that the ubiquitin–
proteasome pathway targets short-lived and abnormal proteins
for proteasomal degradation following ubiquitination.
Rationale — A: Autophagy handles long-lived proteins,
organelles, and bulk degradation, not mainly short-lived
ubiquitinated proteins.
Rationale — C: ERAD is a specialized pathway for misfolded
proteins in the ER but proteasome degrades ubiquitinated
cytosolic substrates broadly.
Rationale — D: The Golgi does not carry out primary
proteasomal degradation of ubiquitinated proteins.
Teaching Point: The ubiquitin–proteasome system clears short-
lived and misfolded cytosolic proteins.
Citation: Robbins & Cotran Pathologic Basis of Disease, 10th
Ed., Chapter 1 — Cellular Housekeeping. ClinicalKey+1
4) Chapter 1 — Cellular Housekeeping
Question: A child with a lysosomal storage disorder
accumulates glycosphingolipids within neurons. Which defect
most directly produces this intracellular accumulation?
A. Impaired proteasome activity
B. Deficient lysosomal hydrolase activity
C. Mitochondrial oxidative phosphorylation failure
D. Excessive autophagic flux
Correct Answer: B
