Cuestionario: Genetic Mutations and Syndromes — 20 preguntas

1. What distinguishes a genetic mutation from a transient change in gene expression?

A. A mutation is a temporary expression change, whereas gene-expression changes permanently alter DNA

B. A mutation affects only proteins, whereas gene-expression changes affect only chromosomes

C. A mutation is a permanent DNA-sequence alteration, whereas gene-expression changes may be temporary

D. A mutation occurs only in body cells, whereas gene-expression changes occur only in germ cells

Answer: (C)

Explicación

A genetic mutation is a permanent alteration of the DNA sequence. In contrast, a transient change in gene expression does not permanently alter the DNA sequence.

2. Which statement correctly compares germ-cell and somatic-cell mutations?

A. Germ-cell mutations occur only after birth, whereas somatic-cell mutations occur only before birth

B. Both mutation types are equally likely to be transmitted to offspring

C. Somatic-cell mutations are inherited, whereas germ-cell mutations arise from environmental factors in body cells

D. Germ-cell mutations may be inherited, whereas somatic-cell mutations arise in body cells and are generally not transmitted to offspring

Answer: (D)

Explicación

Mutations in germ cells can enter the genetic material of offspring. Somatic mutations arise in body cells, sometimes because of factors such as radiation, and generally are not inherited.

3. A point mutation replaces a purine with a pyrimidine. What type of substitution is this?

A. A transition

B. A splice-site mutation

C. A frameshift

D. A transversion

Answer: (D)

Explicación

A transversion replaces a purine with a pyrimidine or vice versa. A transition occurs within the same base class, such as purine-to-purine.

4. A DNA mutation changes a codon so that it specifies a different amino acid without creating a stop codon. Which mutation type is it?

A. A missense mutation

B. A deletion mutation

C. A nonsense mutation

D. A silent mutation

Answer: (A)

Explicación

A missense mutation changes the encoded amino acid. Silent mutations preserve the amino acid, whereas nonsense mutations create an early stop codon.

5. Which mutation directly shifts the way subsequent nucleotides are grouped during translation?

A. A splice-site mutation that leaves mRNA processing unchanged

B. An insertion or deletion that alters the reading frame

C. A silent mutation that preserves the encoded amino acid

D. A point mutation that preserves the reading frame

Answer: (B)

Explicación

Insertions or deletions can shift the reading frame, causing a frameshift mutation. This changes how downstream nucleotides are grouped into codons.

6. Which disorder classification best fits a condition caused by a single gene mutation with a large effect?

A. A complex multigenic disorder

B. A mitochondrial inheritance pattern

C. A chromosomal disorder

D. A Mendelian disorder

Answer: (D)

Explicación

Mendelian disorders result from mutations in a single gene with a large effect. Chromosomal disorders involve chromosome abnormalities, while complex multigenic disorders reflect combined risk from multiple genes.

7. Which inheritance pattern and organ-system involvement characterize Alagille syndrome?

A. An autosomal dominant disorder affecting several systems, including the liver, heart, skeleton, eyes, and kidneys

B. A mitochondrial disorder primarily causing skeletal muscle and retinal disease

C. An autosomal recessive disorder limited primarily to airway cilia and the lungs

D. An X-linked disorder affecting only blood-cell production and the nervous system

Answer: (A)

Explicación

Alagille syndrome is autosomal dominant and can produce liver, skeletal, ocular, cardiac, and renal defects. Primary ciliary dyskinesia, by contrast, is autosomal recessive.

8. Which genetic finding accounts for most cases of Alagille syndrome?

A. A NOTCH2 mutation on chromosome 1p13

B. A JAG1 mutation on chromosome 20p12

C. A mitochondrial DNA deletion

D. A mutation in an X-linked chloride channel gene

Answer: (B)

Explicación

Approximately 95% of Alagille syndrome cases involve mutations in JAG1 on chromosome 20p12. NOTCH2 mutations are associated particularly with renal malformations.

9. Why does Alagille syndrome commonly produce chronic cholestasis?

A. Excessive bile-duct formation increases unconjugated bilirubin and prevents cholesterol synthesis

B. Cardiac defects destroy hepatocytes and cause an isolated rise in unconjugated bilirubin

C. Loss of intrahepatic bile ducts reduces bile flow and causes accumulation of conjugated bilirubin and other liver-related substances

D. Renal dysplasia blocks intestinal absorption of bile acids and directly causes hemolysis

Answer: (C)

Explicación

Loss of intrahepatic bile ducts impairs bile flow, producing chronic cholestasis with increased conjugated bilirubin, liver enzymes, and cholesterol. The disease may progress to cirrhosis or liver failure.

10. Which combination of findings most specifically characterizes McCune–Albright syndrome?

A. Endocrinopathy, renal cysts, and generalized hypopigmentation

B. Fibrous dysplasia, hyperfunctioning endocrinopathy, and unilateral café-au-lait spots

C. Fibrous dysplasia, hepatic disease, and bilateral café-au-lait spots

D. Café-au-lait spots, neurofibromas, and optic pathway tumors

Answer: (B)

Explicación

McCune–Albright syndrome combines fibrous dysplasia, hyperfunctioning endocrinopathy, and unilateral café-au-lait skin spots. Isolated fibrous dysplasia does not require endocrine disease.

11. What genetic mechanism underlies McCune–Albright syndrome?

A. An inherited DNAH5 mutation impairing axonemal dynein arms

B. A postzygotic TCOF1 mutation disrupting neural crest migration

C. A germline GNAS1 mutation producing uniform involvement of all cells

D. A postzygotic GNAS1 mutation producing somatic mosaicism and abnormal Gs alpha signaling

Answer: (D)

Explicación

A postzygotic GNAS1 mutation causes somatic mosaicism and abnormal signaling through the G-protein, cyclic AMP, and adenylate cyclase pathway. Germline mutations are present throughout inherited cell lines.

12. Which radiographic pattern is most consistent with fibrous dysplasia in McCune–Albright syndrome?

A. Symmetric metaphyseal widening with cupping and fraying

B. Multiple punched-out lesions with periosteal reaction and soft-tissue masses

C. Expansile lytic lesions with cortical thinning and a ground-glass appearance

D. Diffuse sclerotic lesions with thickened cortices and a sunburst pattern

Answer: (C)

Explicación

Fibrous dysplasia commonly produces expansile lytic lesions, cortical thinning, and a ground-glass appearance; the proximal femur may develop a shepherd’s-crook deformity.

13. Which endocrine abnormality can occur as a manifestation of McCune–Albright syndrome?

A. Primary adrenal insufficiency

B. Hypoparathyroidism

C. Central diabetes insipidus

D. Precocious puberty

Answer: (D)

Explicación

Endocrine manifestations of McCune–Albright syndrome include hyperthyroidism, Cushing’s syndrome, growth-hormone excess, renal phosphate wasting, and precocious puberty.

14. What best defines primary ciliary dyskinesia?

A. A congenital disorder of alveolar development causing isolated pulmonary restriction

B. An acquired inflammatory disorder causing temporary ciliary slowing after infection

C. A congenital autosomal recessive disorder causing defective ciliary motility and impaired mucociliary clearance

D. An autosomal dominant disorder causing excessive mucus production without ciliary defects

Answer: (C)

Explicación

Primary ciliary dyskinesia is congenital and autosomal recessive, with defective ciliary motility that impairs mucociliary clearance and decreases fertility. Secondary ciliary dysfunction is acquired.

15. How does abnormal ciliary movement produce the major clinical features of primary ciliary dyskinesia?

A. It causes excessive ciliary motion, leading to airway collapse and infertility from gonadal failure

B. It prevents effective clearance and movement, causing recurrent infections, bronchiectasis, and reduced fertility

C. It increases airway clearance but blocks pulmonary surfactant secretion, causing restrictive lung disease

D. It disrupts alveolar macrophages, producing recurrent infections without affecting reproductive function

Answer: (B)

Explicación

Immotile or abnormally moving cilia impair respiratory clearance, causing recurrent infections, chronic rhinosinusitis, and bronchiectasis, while also impairing fallopian-tube cilia and sperm flagella.

16. Which combination defines Kartagener syndrome?

A. Situs inversus, recurrent meningitis, and pulmonary hypertension

B. Bronchiectasis, congenital deafness, and severe asthma

C. Cystic kidneys, chronic sinusitis, and pulmonary fibrosis

D. Situs inversus, chronic sinusitis, and bronchiectasis

Answer: (D)

Explicación

Kartagener syndrome is the combination of situs inversus, chronic sinusitis, and bronchiectasis occurring in primary ciliary dyskinesia.

17. Which description best identifies Treacher Collins syndrome?

A. A congenital disorder characterized primarily by defective ciliary motility

B. A severe genetic disorder of craniofacial development, also called mandibulofacial dysostosis

C. A multisystem disorder dominated by hepatic disease and abnormal bile ducts

D. A neural-tube disorder causing isolated spinal and cranial abnormalities

Answer: (B)

Explicación

Treacher Collins syndrome is a severe genetic disorder of craniofacial development and is also known as mandibulofacial dysostosis or Franceschetti–Zwahlen–Klein syndrome.

18. How does a TCOF1 mutation contribute to the craniofacial abnormalities of Treacher Collins syndrome?

A. A collagen defect directly disrupts bone mineralization without affecting neural crest development

B. Excessive treacle production increases ribosome biogenesis and causes neural crest overgrowth

C. Treacle insufficiency impairs ribosome biogenesis, causing neuroepithelial apoptosis and reduced neural crest cells

D. Dynein-arm dysfunction blocks mucociliary clearance and secondarily reduces neural crest cells

Answer: (C)

Explicación

A TCOF1 mutation causes treacle-protein insufficiency, impaired ribosome biogenesis, neuroepithelial apoptosis, and reduced neural crest cells, leading to branchial-arch anomalies.

19. Which inheritance pattern is characteristic of Treacher Collins syndrome?

A. X-linked recessive inheritance with disease limited to males

B. Mitochondrial inheritance with transmission through affected fathers

C. Autosomal recessive inheritance with complete penetrance in every affected family

D. Autosomal dominant inheritance with variable penetrance, with about 60% of cases spontaneous

Answer: (D)

Explicación

Treacher Collins syndrome is autosomal dominant with variable penetrance, and approximately 60% of cases arise spontaneously.

20. Which combination of physical findings is most typical of Treacher Collins syndrome?

A. Frontal bossing, widely spaced eyes, enlarged hands, and thickened skin

B. Macroglossia, umbilical hernia, generalized overgrowth, and neonatal hypoglycemia

C. Mandibular and zygomatic hypoplasia, downslanting eyelids, lower-eyelid coloboma, and malformed ears

D. Café-au-lait spots, neurofibromas, optic tumors, and tibial bowing

Answer: (C)

Explicación

Typical findings include mandibular and zygomatic hypoplasia, retrognathia, downslanting eyelids, lower-eyelid coloboma, malformed ears, palatal abnormalities, and dental defects.