Genetics & Disease: Muscular Dystrophy, CF, OmpathStudy

--- Q1. A 25-year-old man presents with progressive muscle weakness. Genetic testing reveals a mutation in the dystrophin gene on the X chromosome. Which best explains why this mutation leads to disease? a. Loss of DNA repair capacity leading to increased mutations b. Defective structural protein disrupting muscle cell membrane stability c. Defective enzyme causing substrate accumulation in lysosomes d. Failure of apoptosis leading to accumulation of abnormal myocytes e. Impaired immune surveillance against abnormal muscle fibers Answer: b Dystrophin is a structural protein anchoring the muscle cytoskeleton to the cell membrane; its absence (Duchenne muscular dystrophy) causes membrane fragility, progressive muscle fiber damage, and weakness. --- Q2. A 4-year-old girl presents with recurrent lung infections and pancreatic insufficiency. Sweat chloride test is positive. This autosomal recessive disorder is caused by mutations in which gene? a. FBN1 (fibrillin-1) b. CFTR (chloride channel regulator) c. HBB (β-globin) d. RB1 (retinoblastoma) e. LDLR (low-density lipoprotein receptor) Answer: b Classic presentation of cystic fibrosis, caused by CFTR mutations affecting chloride ion transport. --- Q3. A 16-year-old boy is tall, with long extremities and hyperflexible joints. Echocardiography shows aortic root dilatation. Which genetic defect best explains this patient's condition? a. Mutation in fibrillin-1 leading to defective microfibrils b. Mutation in collagen type III leading to vascular fragility c. Mutation in elastin gene leading to defective elastic fibers d. Mutation in dystrophin gene leading to sarcolemma instability e. Mutation in keratin gene leading to blistering skin disorder Answer: a Classic Marfan syndrome presentation, caused by FBN1 mutations affecting the fibrillin-1 microfibril network that normally sequesters TGF-β and supports connective tissue/aortic wall integrity. --- Q4. A 52-year-old woman with obesity and hypertension develops type 2 diabetes mellitus. Which of the following best describes the genetic basis of this disorder? a. Single gene defect inherited in Mendelian fashion b. Polygenic inheritance with environmental influence c. X-linked recessive mutation in a metabolic enzyme d. Deletion of a chromosomal segment e. Trisomy of chromosome 21 Answer: b Type 2 diabetes is a classic complex/multifactorial disease — the result of many gene variants interacting with environmental factors (diet, obesity, sedentary lifestyle), not a single-gene or chromosomal disorder. --- Q5. A 34-year-old woman with a strong family history of early-onset breast cancer seeks genetic counseling. Which of the following is the most appropriate indication for genetic testing in this patient? a. Sporadic breast cancer at age 70 b. Bilateral breast cancer in her grandmother at age 80 c. Multiple relatives with BRCA-associated cancers at young ages d. A cousin with lung cancer linked to smoking e. Family history of diabetes and hypertension Answer: c Multiple relatives with early-onset, BRCA-spectrum cancers (breast, ovarian) is the classic red flag warranting hereditary cancer genetic testing — late-onset/sporadic cases and unrelated cancer types are not indications. --- Q6. Which of the following best illustrates the use of genetics in predictive medicine ? a. Newborn screening for phenylketonuria b. Karyotyping in suspected Down syndrome c. BRCA1 gene testing in healthy women with family history of breast cancer d. Prenatal ultrasonography e. Blood grouping before transfusion Answer: c Predictive genetic testing identifies future disease risk in currently healthy/asymptomatic individuals based on genetic predisposition — exactly what BRCA1 testing does. PKU screening and Down syndrome karyotyping are diagnostic (detecting existing disease), not predictive. --- Q7. Gene therapy aims to: a. Remove chromosomal abnormalities b. Replace or repair defective genes in somatic cells c. Prevent nondisjunction during meiosis d. Produce vaccines e. Stimulate immune recognition of tumours Answer: b Gene therapy's core goal is correcting/replacing a defective gene's function within somatic cells of the affected individual. --- Q8. A child born to phenotypically normal parents develops cystic fibrosis. The inheritance pattern is most consistent with: a. Autosomal dominant b. Autosomal recessive c. X-linked recessive d. X-linked dominant e. Mitochondrial Answer: b Both unaffected (carrier) parents having an affected child is the hallmark of autosomal recessive inheritance — consistent with CF's known genetics. --- Q9. If a couple are carriers of an autosomal recessive trait, what is the probability that all four of their children will be homozygous for the disease? a. 100% b. 25% c. ¼ × ¼ × ¼ × ¼ d. 1 − (¼+¼+¼+¼) e. ¼ + ¼ + ¼ + ¼ Answer: c Each child independently has a ¼ chance of being homozygous affected; the probability all four are affected is the product of four independent ¼ probabilities. --- Q10. Which of the f