Ch 06

Question 1

A 6-year-old girl presents to the pediatric clinic with severe developmental delays, ataxia, seizures, and frequent inappropriate laughter. Genetic testing reveals a deletion on chromosome 15q11-q13, but the karyotype is normal. As the APRN, you suspect an imprinting disorder.

Which epigenetic mechanism is most likely responsible for her condition?
A. Hypermethylation of the maternal allele, leading to loss of UBE3A expression
B. Hypomethylation of the paternal allele, causing overexpression of SNRPN
C. Histone acetylation promoting euchromatin in the deleted region
D. miRNA-mediated degradation of imprinted mRNAs from both parents

Answer 1

Answer: A. Hypermethylation of the maternal allele, leading to loss of UBE3A expression

This vignette describes Angelman syndrome, where the maternal allele is silenced or deleted, often via hypermethylation. Option B is a trap as it reverses parental roles and references SNRPN (relevant to Prader-Willi). Option C confuses acetylation (which activates genes) with the silencing needed here. Option D misapplies miRNA, which fine-tunes but isn’t primary in imprinting.

Teaching Point: In pediatric NP practice, differentiate Angelman from Prader-Willi via methylation testing. This guides family counseling on recurrence risks and supportive therapies like seizure management, emphasizing epigenetics’ role in non-Mendelian inheritance.

Question 2

A 45-year-old woman with a history of smoking presents with fatigue and anemia. Bone marrow biopsy confirms myelodysplastic syndrome (MDS). Molecular analysis shows hypermethylation of tumor-suppressor gene promoters.
What is the most appropriate epigenetic-targeted therapy to consider?

A. Histone deacetylase inhibitors to tighten chromatin and silence oncogenes
B. DNA demethylating agents like azacitidine to reactivate silenced genes
C. miRNA mimics to overexpress regulatory RNAs in hematopoietic cells
D. Folate supplements to induce hypomethylation across the genome

Answer 2

Answer: B. DNA demethylating agents like azacitidine to reactivate silenced genes

Rationale: In MDS, hypermethylation silences suppressors; azacitidine reverses this, as per the chapter. Option A traps by reversing HDAC inhibitors’ action (they loosen chromatin). Option C confuses miRNA therapy (experimental, not first-line). Option D misuses folate (supports methylation, not hypo-).

Teaching Point: For oncology NPs, monitor azacitidine side effects like nausea; so what? Epigenetic therapies offer options for chemo-resistant patients, highlighting the need for personalized medicine based on molecular profiles.

Question 3

During a prenatal visit, a 32-year-old pregnant woman asks about preventing neural tube defects in her fetus. You discuss folate supplementation. Which epigenetic mechanism does folate primarily influence to reduce this risk?

A. Histone acetylation, enhancing neural gene expression
B. DNA methylation, providing methyl groups for stable gene silencing
C. miRNA biogenesis, regulating developmental transcripts
D. Chromatin remodeling, loosening histones in embryonic stem cells

Answer 3

Answer: B. DNA methylation, providing methyl groups for stable gene silencing

Rationale: Folate is a methyl donor supporting DNA methylation, crucial for neural development. Option A traps with acetylation (unrelated to folate). Option C mislinks to miRNA (not folate-dependent). Option D confuses general remodeling.

Teaching Point: In women’s health NP practice, prescribe prenatal vitamins early. This prevents epigenetic disruptions, reducing birth defects and informing counseling on nutrition’s intergenerational impact.

Question 4

A 28-year-old man with a history of childhood trauma presents with PTSD symptoms. Epigenetic studies show hypermethylation of the NR3C1 gene promoter. What does this finding most likely indicate?

A. Increased glucocorticoid receptor expression, heightening stress response
B. Decreased glucocorticoid receptor expression, impairing stress regulation
C. Histone modifications activating inflammatory pathways
D. miRNA suppression of serotonin transporters

Answer 4

Answer: B. Decreased glucocorticoid receptor expression, impairing stress regulation

Rationale: Hypermethylation silences NR3C1, reducing receptors and dysregulating HPA axis, as in trauma-linked mental health. Option A reverses the effect (hyper- silences). Option C shifts to histones (secondary). Option D traps with serotonin (unrelated gene).

Teaching Point: Psych NPs should screen for ACEs; so what? Epigenetics validates trauma-informed care, guiding therapies like mindfulness to potentially reverse marks and improve outcomes.

Question 5

In a geriatric clinic, a 75-year-old nonsmoking twin presents with better cognitive function than his smoking twin brother. Epigenome analysis reveals differences in global methylation patterns.
What concept best explains this divergence?

A. Somatic mutations accumulating from environmental toxins
B. Epigenetic drift accelerated by lifestyle factors like smoking
C. Telomere elongation in the healthier twin
D. Mitochondrial DNA hypermethylation in the smoker

Answer 5

Answer: B. Epigenetic drift accelerated by lifestyle factors like smoking

Rationale: Twins diverge via epigenetic drift, where marks accumulate differently due to environment. Option A confuses with genetic mutations. Option C reverses telomere aging (shortening occurs). Option D misapplies mtDNA (not primary).

Teaching Point: Geriatric NPs promote smoking cessation; so what? This slows epigenetic aging, reducing dementia risk and emphasizing lifestyle interventions in twin/family counseling.

Question 6

A newborn female infant shows mosaic patterns in skin pigmentation. Genetic testing confirms X-chromosome inactivation issues.
Which epigenetic process is disrupted?
A. Random DNA methylation silencing one X in each cell
B. Histone deacetylation activating both X chromosomes
C. miRNA targeting of Xist RNA for dosage compensation
D. Imprinting of X-linked genes from the paternal allele

Answer 6

Answer: A. Random DNA methylation silencing one X in each cell

Rationale: X-inactivation uses methylation via Xist to silence one X randomly. Option B traps by reversing deacetylation (silences). Option C misuses miRNA (Xist is lncRNA). Option D confuses with autosomal imprinting.

Teaching Point: In primary care, recognize X-linked mosaicism; so what? This aids diagnosis of conditions like fragile X, guiding genetic referrals and family planning.

Question 7

A patient with colorectal cancer has MLH1 gene silencing without mutations. Biopsy shows promoter hypermethylation.
What is the implicated epigenetic mechanism?

A. Histone methylation compacting chromatin around oncogenes
B. DNA hypermethylation repressing mismatch repair genes
C. miRNA upregulation promoting cell proliferation
D. Acetylation loosening tumor-suppressor promoters

Answer 7

Answer: B. DNA hypermethylation repressing mismatch repair genes

Rationale: Hypermethylation silences MLH1, impairing repair (chapter example). Option A shifts to histones/onco-. Option C traps with miRNA (secondary). Option D reverses acetylation.

Teaching Point: Oncology NPs order MSI testing; so what? Epigenetic silencing informs targeted therapies, improving prognosis through early intervention.

Question 8

A 50-year-old man with alcohol use disorder has a child with fetal alcohol spectrum disorder. Epigenetic analysis shows altered histone acetylation in the child’s brain genes.
What does this suggest?
A. Paternal hypomethylation transmitting addiction risk
B. In utero exposure disrupting histone modifications for development
C. miRNA from sperm affecting embryonic gene expression
D. Imprinted genes from mother silenced by alcohol

Answer 8

Answer: B. In utero exposure disrupting histone modifications for development

Rationale: Ethanol alters histones, affecting neurodevelopment. Option A confuses parental transmission. Option C misapplies miRNA/sperm. Option D reverses imprinting.

Teaching Point: Family NPs screen for substance use in pregnancy; so what? This prevents epigenetic harm, linking to education on reversible lifestyle impacts.

Question 9

During a well-child visit, parents of a 4-year-old ask about obesity risks. The grandmother experienced famine during pregnancy.
What epigenetic change might increase the child’s risk?

A. Hypermethylation of leptin genes from maternal line
B. Hypomethylation of IGF2, promoting growth and fat storage
C. Histone deacetylation silencing appetite suppressors
D. miRNA downregulation of metabolic regulators

Answer 9

Answer: B. Hypomethylation of IGF2, promoting growth and fat storage

Rationale: Dutch Hunger Winter shows IGF2 hypomethylation in offspring (chapter). Option A reverses methylation. Option C traps with histones. Option D misuses miRNA.

Teaching Point: Pediatric NPs assess intergenerational histories; so what? Recommend nutrition counseling to mitigate risks, breaking epigenetic cycles.

Question 10

A 60-year-old woman with breast cancer has BRCA1 promoter methylation but no family history.
What therapy targets this epigenetic alteration?
A. HDAC inhibitors to acetylate histones
B. Demethylating agents like decitabine to restore expression
C. miRNA antagonists to block oncogenic RNAs
D. Folate antagonists to induce hypermethylation

Answer 10

Answer: B. Demethylating agents like decitabine to restore expression

Rationale: Demethylators reverse BRCA1 silencing. Option A confuses HDAC (for histones). Option C traps with miRNA. Option D reverses folate role.

Teaching Point: Women’s health NPs use epigenetic screening; so what? This personalizes treatment, avoiding unnecessary aggressive therapies.

Question 11

In a mental health clinic, a patient with depression has hypermethylated BDNF promoters after chronic stress.
What does this indicate?

A. Increased neurotrophic factor, worsening symptoms
B. Decreased neurotrophic factor, impairing neuroplasticity
C. Histone changes activating inflammatory cytokines
D. miRNA enhancing synaptic proteins

Answer 11

Answer: B. Decreased neurotrophic factor, impairing neuroplasticity

Rationale: Hypermethylation silences BDNF, linking stress to depression. Option A reverses. Option C shifts to histones. Option D traps with miRNA.

Teaching Point: Psych NPs integrate stress management; so what? Epigenetics supports exercise prescriptions to reverse marks, enhancing therapy efficacy.

Question 12

A fetus exposed to maternal smoking shows altered lung gene expression via epigenetic changes. Which mechanism is most likely?

A. DNA hypomethylation activating nicotine receptors
B. Histone acetylation promoting inflammatory genes
C. miRNA silencing developmental transcription factors
D. Imprinting defects in placental genes

Answer 12

Answer: B. Histone acetylation promoting inflammatory genes

Rationale: Smoking alters histones, activating harmful genes (chapter). Option A confuses hypo-. Option C traps with miRNA. Option D misapplies imprinting.

Teaching Point: Prenatal NPs counsel on smoking cessation; so what? Prevents long-term respiratory issues, emphasizing environmental epigenetics.

Question 13

An elderly patient asks about anti-aging diets. You explain how caloric restriction affects epigenetics.
What is the key mechanism?

A. Increased DNA methylation closing longevity genes
B. Histone deacetylation mimicking sirtuin activation
C. miRNA upregulation suppressing age-related inflammation
D. Hypomethylation opening telomerase promoters

Answer 13

Answer: B. Histone deacetylation mimicking sirtuin activation

Rationale: Restriction deacetylates histones, extending lifespan (chapter analogy). Option A reverses. Option C traps with miRNA. Option D confuses telomeres.

Teaching Point: Geriatric NPs recommend balanced diets; so what? Slows epigenetic drift, reducing chronic disease burden.

Question 14

A child with Prader-Willi syndrome has a uniparental disomy of chromosome 15. What epigenetic error occurred?

A. Maternal disomy with hypermethylation silencing paternal-like expression
B. Paternal disomy with hypomethylation activating maternal genes
C. Histone modifications overriding imprinting centers
D. miRNA from disomic alleles degrading SNRPN

Answer 14

Answer: A. Maternal disomy with hypermethylation silencing paternal-like expression

Rationale: Maternal disomy means both copies methylated as maternal, silencing key genes. Option B reverses. Option C traps with histones. Option D misuses miRNA.

Teaching Point: Pediatric NPs manage with growth hormone. Epigenetics informs prognosis and behavioral interventions.

Question 15

In leukemia, TET2 mutations lead to abnormal DNA methylation patterns. What is the result?

A. Hypermethylation due to increased methyltransferase activity
B. Hypomethylation from impaired hydroxymethylation
C. Histone acetylation enhancing leukemic stem cells
D. miRNA dysregulation promoting blast proliferation

Answer 15

Answer: B. Hypomethylation from impaired hydroxymethylation

Rationale: TET2 oxidizes methyl groups; mutations cause hypo- (chapter). Option A reverses. Option C traps with histones. Option D misuses miRNA.

Teaching Point: Oncology NPs monitor TET2 status; so what? Guides use of hypomethylating agents like azacitidine.

Question 16

A child has a deletion on chromosome 15q. When inherited from the father, the child develops hypotonia, hyperphagia, and obesity. When inherited from the mother, the child develops severe intellectual disability, ataxia, and seizures. Which mechanism best explains this difference in phenotype?

A. Autosomal recessive inheritance
B. X-chromosome inactivation
C. Genomic imprinting
D. Variable penetrance

Answer 16

C. Genomic imprinting

Rationale

Genomic imprinting results in parent-of-origin–specific gene expression. One parental allele is epigenetically silenced. Loss of the active allele leads to disease. In chromosome 15q disorders, paternal loss produces Prader–Willi syndrome, while maternal loss produces Angelman syndrome.

Teaching Point

👉 If phenotype depends on which parent transmitted the allele, think imprinting first.

Question 17

Which inheritance pattern is ruled out by the presence of father-to-son transmission?

A. Autosomal dominant
B. Autosomal recessive
C. X-linked recessive
D. Genomic imprinting

Answer 17

C. X-linked recessive

Rationale

Fathers pass a Y chromosome to sons, not an X chromosome. Therefore, father-to-son transmission cannot occur in X-linked disorders.

Teaching Point

👉 Father → son transmission excludes X-linked inheritance.

Question 18

A female patient has mild symptoms of a disorder that is typically severe in males. Which mechanism best explains this finding?

A. Reduced penetrance
B. Variable expressivity
C. Skewed X-chromosome inactivation
D. Autosomal dominance

Answer 18

C. Skewed X-chromosome inactivation

Rationale

Random X-inactivation produces mosaic expression of X-linked genes. If inactivation favors the normal or abnormal allele, symptom severity varies.

Teaching Point

👉 Female variability in X-linked disease = X-inactivation mosaicism.

Question 19

Dense methylation of CpG islands in a gene promoter most directly leads to which effect?

A. Increased transcription
B. Increased translation
C. Transcriptional silencing
D. Frameshift mutation

Answer 19

C. Transcriptional silencing

Rationale

Promoter methylation blocks transcription factor binding and recruits repressor proteins, preventing transcription.

Teaching Point

👉 Methylated promoter = gene OFF.

Question 20

Two siblings are affected by the same disorder. Both parents are unaffected. Both sexes are equally affected. The parents are first cousins. Which inheritance pattern is most likely?

A. Autosomal dominant
B. Autosomal recessive
C. X-linked recessive
D. Genomic imprinting

Answer 20

B. Autosomal recessive

Rationale

Autosomal recessive disorders require two abnormal alleles. Consanguinity increases the likelihood of shared recessive mutations.

Teaching Point

👉 Consanguinity + unaffected parents = recessive until proven otherwise.

Question 21

Which finding most strongly suggests genomic imprinting?

A. Incomplete penetrance
B. Variable expressivity
C. Parent-of-origin–specific phenotype
D. Vertical transmission

Answer 21

C. Parent-of-origin–specific phenotype

Rationale

Imprinting disorders manifest differently depending on whether the allele is inherited maternally or paternally.

Teaching Point

👉 Imprinting = “Which parent?” matters.

Question 22

Which epigenetic process produces mosaic patterns of gene expression in females?

A. DNA methylation
B. Histone acetylation
C. X-chromosome inactivation
D. miRNA degradation

Answer 22

C. X-chromosome inactivation

Rationale

Random inactivation of one X chromosome in early embryogenesis creates cellular mosaicism.

Teaching Point

👉 Patchy female phenotypes = X-inactivation.

Question 23

A tumor suppressor gene is transcriptionally silent, but no coding mutation is identified. Which mechanism best explains this finding?

A. Frameshift mutation
B. Nonsense mutation
C. Promoter hypermethylation
D. Chromosomal translocation

Answer 23

C. Promoter hypermethylation

Rationale

Epigenetic hypermethylation can silence genes without altering DNA sequence.

Teaching Point

👉 Normal gene + no expression = epigenetic silencing.

Question 24

Which statement about epigenetic changes is most accurate?

A. They permanently alter DNA
B. They occur only prenatally
C. They are potentially reversible
D. They affect only germ cells

Answer 24

C. They are potentially reversible

Rationale

Epigenetic modifications can be altered by medications and environmental changes.

Teaching Point

👉 Reversibility is why epigenetics matters clinically.

Question 25

A disorder primarily affects males, shows variable severity in females, and demonstrates no father-to-son transmission. Which inheritance pattern is most likely? A. Autosomal dominant B. Autosomal recessive C. X-linked D. Genomic imprinting

Answer 25

C. X-linked Rationale This classic pattern reflects X-linked inheritance with female mosaicism. Teaching Point 👉 Male predominance + no father-son = X-linked.

Question 26

Which feature best distinguishes imprinting disorders from autosomal recessive disorders? A. Autosomal location B. Two abnormal alleles required C. Parent-of-origin–specific expression D. Childhood onset

Answer 26

C. Parent-of-origin–specific expression Rationale Imprinting involves monoallelic expression based on parental origin, not two mutated alleles. Teaching Point 👉 One allele silenced by design = imprinting.

Question 27

Which epigenetic change is most commonly associated with oncogene activation? A. Promoter hypermethylation B. Global hypomethylation C. Histone deacetylation D. miRNA overexpression

Answer 27

B. Global hypomethylation Rationale Loss of methylation activates normally silenced oncogenes and destabilizes the genome. Teaching Point 👉 Hypomethylation = oncogenes ON.

Question 28

Which laboratory technique is used to identify DNA methylation patterns? A. PCR B. Bisulfite conversion C. Western blot D. Southern blot

Answer 28

B. Bisulfite conversion Rationale Bisulfite converts unmethylated cytosines to uracil, allowing methylation mapping. Teaching Point 👉 Bisulfite = methylation gold standard.

Question 29

A disorder appears in every generation and affects males and females equally. Which inheritance pattern is most likely? A. Autosomal recessive B. X-linked recessive C. Autosomal dominant D. Genomic imprinting

Answer 29

C. Autosomal dominant Rationale Autosomal dominant disorders show vertical transmission and equal sex distribution. Teaching Point 👉 Vertical + equal sexes = dominant.

Question 30

Which mechanism best explains why identical twins may develop different diseases in adulthood? A. Mutation accumulation B. Meiotic recombination C. Environmental epigenetic divergence D. Germline mosaicism

Answer 30

C. Environmental epigenetic divergence Rationale Environmental exposures modify methylation and chromatin patterns over time, altering gene expression. Teaching Point 👉 Same DNA ≠ same phenotype over time.

Question 31

Which gene is often seen in retinoblastoma? MLH1 RB1 BRCA1 BRCA2

Answer 31

RB1 Hypermethylation of the promoter region on the RB1 gene is often seen in retinoblastoma. An inherited form of colon cancer is related to methylation of the promoter region of the MLH1 gene. The BRCA1 and BRCA2 genes are observed in some cases of inherited breast cancer.

Question 32

5-Azacytidine has been used as a therapeutic drug in the treatment of which disease process? Leukemia Brain cancer Benign neoplasm Type II diabetes

Answer 32

Leukemia 5-Azacytidine, a demethylating agent, has been used as a therapeutic drug in the treatment of leukemia and myelodysplastic syndrome. 5-Azacytidine is not a therapeutic drug used in the treatment of brain cancer, benign neoplasm, or type II diabetes.

Question 33

Which characteristic supports the diagnosis of Angelman syndrome? Short stature, hypotonia, obesity Large size, creases on the earlobe, large tongue Growth retardation, leg length discrepancy, small face Severe mental retardation, seizures, ataxia Angelman syndrome is characterized by severe mental retardation, seizures, and ataxia. Prader-Willi syndrome is characterized by short stature, hypotonia, and obesity. Beckwith-Wiedemann syndrome is characterized by large size for gestational age, creases on the earlobe, and a large tongue. Russel-Silver syndrome is characterized by growth retardation, leg length discrepancy, and a small, triangular-shaped face.

Answer 33

Severe mental retardation, seizures, ataxia Angelman syndrome is characterized by severe mental retardation, seizures, and ataxia. Prader-Willi syndrome is characterized by short stature, hypotonia, and obesity. Beckwith-Wiedemann syndrome is characterized by large size for gestational age, creases on the earlobe, and a large tongue. Russel-Silver syndrome is characterized by growth retardation, leg length discrepancy, and a small, triangular-shaped face.

Question 34

Children with Beckwith-Wiedemann syndrome are at risk for the development of Wilms tumor. rectal cancer. diabetes. pulmonary fibrosis.

Answer 34

Wilms tumor. Children with Beckwith-Wiedemann syndrome are at an increased risk for the development of Wilms tumor or hepatoblastoma. Rectal cancer, diabetes, and pulmonary fibrosis are not associated with Beckwith-Wiedemann syndrome.

Question 35

Which is true regarding epigenetic modifications? They alter gene expression by modifying DNA. They can modulate behavior later in life. They occur only at the time of birth. They at best only involve benign processes.

Answer 35

They can modulate behavior later in life. Exposure to stress early in life can modulate behavior in adulthood. Epigenetic processes can help store information about the environment, and these relevant epigenetic modifications can modulate behavior later in life.

Question 36

Which describe epigenetic mechanisms? DNA methylation, histone modifications, RNA-based modifications RNA methylation, protease modifications, DNA-based modifications Genetic disruption, protease modifications, DNA-based modifications Histone modification, DNA-based modifications, RNA methylation

Answer 36

DNA methylation, histone modifications, RNA-based modifications DNA methylation, histone modifications, RNA-based modifications are epigenetic mechanisms. RNA methylation and protease modifications are not. Additionally, DNA-based modifications although important are not mechanisms of epigenetics.

Question 37

Which statement is correct regarding the epigenetic screening of cancer? Epigenetic screening is no use to cancer detection. Epigenetic screening involves invasive procedures. This is a very expensive alternative to current testing. It can complement current detection methods.

Answer 37

It can complement current detection methods. The common finding of epigenetic alteration in cancerous tissue raises the possibly that epigenetic screening approaches could complement or even replace existing early-detection methods. In some cases, epigenetic screening could be done using bodily fluids, such as urine or sputum, eliminating the need for the more invasive, costly, and risky strategies currently in place.

Question 38

Which features are associated with Prader-Willi syndrome? (Select all that apply.) Short stature Small hands and feet Hypertonia Hypogonadism Mild mental retardation

Answer 38

Short stature Small hands and feet Hypogonadism Mild mental retardation The following are features of a person with Prader-Willi syndrome: short stature, hypotonia, small hands and feet, obesity, hypogonadism, and mild-to-moderate retardation.

Question 39

Which type of cancer is targeted in histone deacetylase inhibitor (HDAC) therapy? (Select all that apply.) Breast Prostate Pancreas Gastric

Answer 39

Breast Prostate Pancreas Histone deacetylase inhibitors (HDACs) are used to treat cancers of the breast, prostate, and pancreas. They have also been used to treat some forms of leukemia and lymphoma that are characterized by transcriptional repression. Gastric cancer is not treated with HDACs.

Question 40

Which steps are involved in chromatin immunoprecipitation (ChIP)? (Select all that apply.) Cross-linking DNA-bound proteins Selecting for proteins of interest Washing away proteins Duplicating nonprotein bound DNA

Answer 40

Cross-linking DNA-bound proteins Selecting for proteins of interest Washing away proteins The steps involved in chromatin immunoprecipitation are cross-linking DNA-bound proteins to genomic regions to which they are attached; lysing DNA regions that are not protein-bound; selecting for proteins of interest; capturing protein DNA-complexes; removing protein DNA cross links and wash away proteins; sequence DNA fragments to profile the portion of genome that was bound by the protein of interest; and repeat to characterize DNAs bound to other proteins of interest.