Genetics and Disease Practice Questions

Q: Which of the following is an autosomal dominant metabolic disorder?

Familial hypercholesterolemia. The correct answer is **Familial Hypercholesterolemia (FH)**. **1. Why Familial Hypercholesterolemia is correct:** FH is a classic example of an **Autosomal Dominant (AD)** metabolic disorder [1]. It is primarily caused by mutations in the **LDLR gene** (encoding the LDL receptor), though mutations in *APOB* or *PCSK9* can also be responsible [1]. Because it is dominant, even heterozygotes (1 in 250 individuals) have significantly elevated LDL levels from birth, leading to premature atherosclerosis and tendon xanthomas [1]. **2. Why the other options are incorrect:** * **Cystic Fibrosis (A):** This is the most common lethal **Autosomal Recessive (AR)** disorder in Caucasians, caused by mutations in the *CFTR* gene. * **Phenylketonuria (B):** This is an **Autosomal Recessive** inborn error of metabolism involving a deficiency of the enzyme phenylalanine hydroxylase. * **Alpha-1 Antitrypsin Deficiency (C):** This follows an **Autosomal Recessive** (or more accurately, co-dominant) inheritance pattern. It typically presents with early-onset emphysema and liver cirrhosis. **3. NEET-PG High-Yield Pearls:** * **Rule of Thumb:** Most **enzymatic** deficiencies are Autosomal Recessive, whereas disorders involving **structural proteins or receptors** (like the LDL receptor in FH) are often Autosomal Dominant. * **Clinical Triad of FH:** Elevated LDL-C, Tendon Xanthomas (especially the Achilles tendon), and Arcus Senilis at a young age. * **Other AD Metabolic/Structural Disorders to remember:** Marfan Syndrome, Huntington’s Disease, Neurofibromatosis, and Adult Polycystic Kidney Disease (ADPKD).

Q: Edwards syndrome is associated with which chromosomal abnormality?

Trisomy 18. **Explanation:** **Edwards syndrome** is caused by **Trisomy 18** (an extra copy of chromosome 18). It is the second most common autosomal trisomy among live births, following Down syndrome. The condition is characterized by severe intellectual disability and multi-system defects, with a high mortality rate in the first year of life. **Analysis of Options:** * **Option A (Trisomy 21):** This is **Down syndrome**, the most common chromosomal disorder. Key features include Brushfield spots, simian crease, and increased risk of Alzheimer’s and ALL. * **Option C (Trisomy 13):** This is **Patau syndrome**. It is clinically distinguished by "midline defects" such as holoprosencephaly, cleft lip/palate, and polydactyly. * **Option D (5p deletion):** This is **Cri-du-chat syndrome**. It is characterized by a high-pitched, cat-like cry, microcephaly, and severe developmental delay. **Clinical Pearls for NEET-PG:** To differentiate the trisomies quickly, remember these high-yield physical findings for Edwards syndrome: 1. **Clenched fists** with overlapping fingers (index finger over 3rd, 5th over 4th). 2. **Rocker-bottom feet** (also seen in Patau, but classic for Edwards). 3. **Micrognathia** (small jaw) and low-set malformed ears. 4. **Congenital Heart Disease:** Most commonly VSD or PDA. 5. **Prenatal Screening:** Shows decreased levels of MS-AFP, hCG, and unconjugated estriol (uE3). **Mnemonic:** "Edwards" starts with **E**, and **E**ighteen starts with **E**. Also, think of **E**lection age (18) to remember Trisomy 18.

Q: Adrenomyeloneuropathy, a variant of adrenoleukodystrophy which manifests as adrenal insufficiency beginning in childhood and later develops into a progressive spastic paraparesis, is transmitted as:

X-linked disorder. **Explanation:** **Adrenoleukodystrophy (ALD)** and its adult-onset variant, **Adrenomyeloneuropathy (AMN)**, are caused by mutations in the ***ABCD1* gene** located on the **X chromosome**. This gene encodes the adrenoleukodystrophy protein (ALDP), a peroxisomal membrane transporter required for the breakdown of **Very Long Chain Fatty Acids (VLCFA)**. 1. **Why X-linked is correct:** The *ABCD1* mutation leads to the accumulation of VLCFAs in the plasma and tissues, specifically the adrenal cortex and the white matter of the CNS. Because the gene is located on the X chromosome, the disease follows an **X-linked recessive** inheritance pattern. It primarily affects males, while female carriers may develop milder neurological symptoms later in life. 2. **Why other options are incorrect:** * **Autosomal Dominant/Recessive:** Peroxisomal biogenesis disorders like Zellweger Syndrome are autosomal recessive, but ALD/AMN is strictly linked to the X chromosome. * **Sporadic:** While *de novo* mutations can occur, the condition is a heritable genetic disorder with a predictable transmission pattern. **Clinical Pearls for NEET-PG:** * **Classic Presentation:** A young boy with behavioral changes, vision loss, and skin hyperpigmentation (due to adrenal insufficiency/Addison’s disease). * **AMN Variant:** Presents in the 20s-40s with progressive spastic paraparesis and sphincter dysfunction. * **Diagnosis:** Elevated plasma levels of **VLCFA** (most specific test). * **MRI Finding:** Symmetrical enhancement of the posterior white matter (occipito-parietal region). * **Treatment:** Dietary restriction is ineffective; Hematopoietic Stem Cell Transplant (HSCT) is the treatment of choice in early stages.

Q: Fredrich's ataxia is caused by which type of mutation?

Expanded trinucleotide repeat. **Explanation:** **Friedreich's Ataxia (FRDA)** is an autosomal recessive neurodegenerative disorder. The correct answer is **Expanded Trinucleotide Repeat** because the disease is caused by an unstable expansion of the **GAA** triplet repeat in the first intron of the **FXN gene** on chromosome 9. This expansion leads to transcriptional silencing (epigenetic knockdown) of the gene, resulting in a deficiency of the protein **Frataxin**. Frataxin is essential for mitochondrial iron metabolism; its deficiency leads to iron overload in the mitochondria, causing oxidative stress and cell death, primarily in the dorsal root ganglia, spinal cord, and heart. **Analysis of Incorrect Options:** * **A & C (Point and Missense Mutations):** While point mutations (including missense) can occur in the FXN gene, they account for less than 5% of cases. The hallmark and primary cause (95%+) for NEET-PG purposes is the triplet repeat expansion. * **D (Inversion):** Inversions involve a segment of DNA being reversed end-to-end. This is the classic mechanism for **Hemophilia A** (Factor VIII gene inversion), not Friedreich's Ataxia. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** Autosomal Recessive (unique among most trinucleotide repeat disorders like Huntington’s or Myotonic Dystrophy, which are dominant). * **Repeat Sequence:** **GAA** (Mnemonic: Friedreich is **G**reat **A**t **A**taxia). * **Clinical Triad:** Progressive limb ataxia, loss of position/vibration sense, and absent deep tendon reflexes (especially ankle jerk). * **Most Common Cause of Death:** **Hypertrophic Cardiomyopathy** (HOCM) leading to heart failure or arrhythmias. * **Associated Findings:** Kyphoscoliosis, Pes Cavus (high-arched feet), and Diabetes Mellitus (in ~10-20% of patients).

Q: Non-frameshift mutation of the dystrophin gene causes which of the following conditions?

Becker's Muscular Dystrophy. **Explanation:** The correct answer is **Becker’s Muscular Dystrophy (BMD)**. The underlying medical concept is the **"Reading Frame Hypothesis."** 1. **Why BMD is correct:** Becker’s Muscular Dystrophy is caused by **non-frameshift mutations** (typically in-frame deletions). Because the reading frame is preserved, the cell can still produce a truncated but **partially functional** dystrophin protein. [1] This results in a milder clinical phenotype, later onset (usually >15 years), and a longer life expectancy compared to Duchenne. 2. **Why other options are incorrect:** * **Duchenne Muscular Dystrophy (DMD):** Caused by **frameshift mutations** (or nonsense mutations) that completely disrupt the reading frame. [1] This leads to a total absence of functional dystrophin, resulting in severe, progressive muscle wasting starting in early childhood. * **Myotonic Dystrophy:** This is an autosomal dominant condition caused by **triplet repeat expansions** (CTG repeats in the *DMPK* gene for Type 1), not mutations in the dystrophin gene. * **Limb Girdle Dystrophy (LGMD):** This is a heterogeneous group of disorders caused by mutations in genes encoding **sarcoglycans** [2] or other structural proteins, rather than the dystrophin gene itself. **High-Yield Clinical Pearls for NEET-PG:** * **Dystrophin Gene:** The largest known human gene (located on Xp21), making it highly susceptible to spontaneous mutations. [1] * **Gower’s Sign:** Classic clinical finding in DMD/BMD due to proximal muscle weakness. * **Diagnosis:** Gold standard is genetic testing; Muscle biopsy shows "patchy" dystrophin staining in BMD and "absent" staining in DMD. * **Cause of Death:** Most commonly due to dilated cardiomyopathy or respiratory failure.

Q: Classic form of Alport syndrome is inherited as:

X-linked. Alport syndrome is a primary glomerular disease caused by mutations in the genes encoding **Type IV collagen**, which is a critical structural component of the glomerular basement membrane (GBM), cochlea, and lens. **1. Why X-linked is Correct:** The "classic" and most common form of Alport syndrome (accounting for approximately **80-85% of cases**) is inherited in an **X-linked dominant** fashion. This is due to mutations in the **COL4A5 gene** located on the X chromosome. Because it is X-linked, males are typically more severely affected, often progressing to end-stage renal disease (ESRD), while females (heterozygotes) may have a more variable clinical course ranging from isolated hematuria to renal failure. **2. Why other options are Incorrect:** * **Autosomal Recessive (AR):** This accounts for about 15% of cases and is caused by mutations in *COL4A3* or *COL4A4*. It is seen in clinical practice but is not the "classic" or most frequent form. * **Autosomal Dominant (AD):** This is the rarest form (approx. 5%) and usually presents with a slower progression to renal failure. * **Sporadic:** While de novo mutations can occur in the *COL4A5* gene, Alport syndrome is fundamentally a hereditary genetic disorder, not a sporadic one. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Triad:** Hereditary nephritis (hematuria), Sensorineural hearing loss (high frequency), and Ocular defects (**Anterior Lenticonus** is pathognomonic). * **Electron Microscopy (EM):** Characterized by a "Basket-weave appearance" due to irregular thinning and thickening of the GBM. * **Genetic Defect:** Mutation in alpha-5 chain of Type IV collagen (X-linked). * **Post-Transplant Complication:** Patients with Alport syndrome may develop **Goodpasture-like syndrome** (Anti-GBM disease) after a kidney transplant because their immune system recognizes the normal Type IV collagen in the graft as foreign.

Q: Which of the following statements about Hemochromatosis is true?

Inherited as an autosomal recessive disorder. Explanation: Hereditary Hemochromatosis (HH) is a disorder of iron metabolism characterized by increased intestinal iron absorption, leading to iron deposition in various organs (liver, heart, pancreas, and joints). 1. Why Option D is Correct: The most common form of Hemochromatosis (Type 1) is caused by mutations in the HFE gene (most commonly C282Y) located on Chromosome 6 [2]. It is inherited as an autosomal recessive disorder. This means an individual must inherit two mutated alleles to be at risk for the phenotypic expression of the disease [2]. Both the C282Y and the H63D mutations can be identified by genetic testing, which is now in routine clinical use [1]. 2. Why the Other Options are Incorrect: * Option A: While phlebotomy is the treatment of choice and can normalize life expectancy if started early, it is not "curative" in a genetic sense [1]. The underlying genetic defect remains, and the patient requires lifelong monitoring and maintenance therapy [1]. * Option B: Although the gene frequency is equal in both sexes, the disease is more common in males (approx. 5:1 to 10:1 ratio). Females are "physiologically protected" due to iron loss during menstruation and pregnancy, delaying clinical presentation. * Option C: Hemochromatosis is a classic example of incomplete penetrance. Many individuals homozygous for the C282Y mutation never develop clinical symptoms or significant iron overload [1]. Clinical Pearls for NEET-PG: * Classic Triad (Bronze Diabetes): Cirrhosis, Diabetes Mellitus, and Skin Hyperpigmentation [2]. * Early Sign: Arthropathy (specifically involving the 2nd and 3rd metacarpophalangeal joints). * Diagnosis: Best initial test is Transferrin Saturation (>45%); Gold standard for diagnosis is HFE Gene Analysis [1]. * MRI: Used to quantify hepatic iron (shows low signal intensity on T2-weighted images) [1]. * Most common cause of death: Hepatocellular Carcinoma (HCC) [2].

Q: Which one of the following neurological conditions is not inherited in an autosomal dominant pattern?

Friedreich's ataxia. **Explanation:** The core concept tested here is the mode of inheritance for common genetic syndromes encountered in neurology and medicine. **1. Why Friedreich’s Ataxia is the correct answer:** Friedreich’s ataxia (FA) is an **Autosomal Recessive (AR)** condition. It is the most common inherited ataxia and is caused by a **GAA trinucleotide repeat expansion** in the *FXN* gene on chromosome 9, which encodes the protein **frataxin**. This leads to mitochondrial iron overload and oxidative damage, primarily affecting the spinocerebellar tracts, dorsal columns, and pyramidal tracts [1]. **2. Analysis of Incorrect Options:** * **Neurofibromatosis (Type 1 and 2):** Both are classic examples of **Autosomal Dominant (AD)** inheritance. NF1 is linked to Chromosome 17, and NF2 to Chromosome 22. * **Marfan’s Syndrome:** This is an **AD** connective tissue disorder caused by mutations in the *FBN1* gene (encoding Fibrillin-1) on Chromosome 15. * **Bloom Syndrome:** While the question asks for "neurological conditions," Bloom syndrome is primarily a chromosomal instability disorder. However, it is **Autosomal Recessive**, making it technically a correct answer alongside Friedreich's ataxia. *Note: In standard NEET-PG patterns, if two options are AR, Friedreich's ataxia is the "more" neurological choice.* **3. High-Yield Clinical Pearls for NEET-PG:** * **Friedreich’s Ataxia Triad:** Progressive ataxia, HOCM (Hypertrophic Obstructive Cardiomyopathy), and Diabetes Mellitus. Skeletal deformities like **Pes Cavus** and Kyphoscoliosis are common. * **Trinucleotide Repeat Mnemonic:** "GAA" for Friedreich’s Ataxia (**G**ait **A**taxia **A**lways). * **Most AD conditions** involve structural protein defects (e.g., Marfan, NF, Achondroplasia). * **Most AR conditions** involve enzyme deficiencies or metabolic pathways [2] (e.g., Wilson’s disease, Hemochromatosis, FA).

Q: Mental retardation is NOT a feature of which of the following mucopolysaccharidoses?

Sanfilippo syndrome (MPS III). The correct answer is **D. Morquio syndrome (MPS IV)**. (Note: The provided key in the prompt incorrectly marks Sanfilippo; however, clinically and for NEET-PG, Morquio is the classic MPS characterized by **normal intelligence**). **1. Why Morquio Syndrome (MPS IV) is the correct answer:** In Mucopolysaccharisoses (MPS), mental retardation occurs when there is an accumulation of heparan sulfate in the CNS. Morquio syndrome is caused by a deficiency of *Galactose-6-sulfatase* (Type A) or *Beta-galactosidase* (Type B), leading to the accumulation of **Keratan sulfate** [1]. Since Keratan sulfate is not a primary component of the brain, patients with Morquio syndrome typically have **normal intelligence**. They are characterized by severe skeletal dysplasia (spondyloepiphyseal dysplasia) and ligamentous laxity. **2. Why the other options are incorrect:** * **Hurler Syndrome (MPS I):** This is the most severe form. It involves the accumulation of dermatan and heparan sulfate, leading to progressive developmental delay and significant cognitive impairment [1]. * **Hunter Syndrome (MPS II):** This is X-linked recessive. Like Hurler, it involves heparan sulfate accumulation, leading to mental retardation [1]. * **Sanfilippo Syndrome (MPS III):** This syndrome is unique because it presents with **severe CNS involvement** and behavioral disturbances, while the physical (somatic) features are relatively mild. Mental retardation is a hallmark feature [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Normal Intelligence:** Morquio (MPS IV) and Scheie Syndrome (MPS IS) [1]. * **No Corneal Clouding:** Hunter Syndrome (MPS II) – "The Hunter needs clear eyes to see the target." * **X-linked Recessive:** Hunter Syndrome (All other MPS are Autosomal Recessive). * **Diagnosis:** Initial screening via urinary GAGs; confirmed by enzyme assay or genetic testing.

Q: Duchenne's muscular dystrophy is inherited in which pattern?

X-linked recessive. **Explanation:** **Duchenne Muscular Dystrophy (DMD)** is caused by a mutation in the **DMD gene** located on the short arm of the **X chromosome (Xp21)**. This gene encodes for **dystrophin**, a critical protein that links the cytoskeleton of a muscle fiber to the surrounding extracellular matrix. 1. **Why X-linked Recessive (Correct):** DMD follows an X-linked recessive pattern because the gene is located on the X chromosome [1]. Since males have only one X chromosome (XY), a single mutated copy results in the disease. Females (XX) are typically asymptomatic carriers because their second, healthy X chromosome produces sufficient dystrophin. 2. **Why other options are incorrect:** * **X-linked Dominant:** In this pattern, both males and females would be affected if they carry just one copy of the mutation (e.g., Alport Syndrome). In DMD, females are generally spared from severe clinical symptoms. * **Autosomal Dominant/Recessive:** These involve mutations on non-sex chromosomes (1-22). DMD is specifically linked to the sex-determining X chromosome. **High-Yield Clinical Pearls for NEET-PG:** * **The Gene:** The DMD gene is the **largest known human gene**, making it highly susceptible to spontaneous mutations (30% of cases are *de novo*). * **Clinical Signs:** Look for **Gower’s sign** (using hands to "climb up" the legs to stand) and **pseudohypertrophy of the calves** (fatty replacement of muscle). * **Diagnosis:** Initial screen shows highly elevated **Creatine Kinase (CK)** levels. Gold standard is **Genetic Testing** (MLPA); Muscle biopsy shows absent dystrophin. * **Becker Muscular Dystrophy (BMD):** Also X-linked recessive but milder, caused by *in-frame* mutations resulting in truncated (partially functional) dystrophin.

Question 1

Which of the following is an autosomal dominant metabolic disorder?

Accepted Answer

Familial hypercholesterolemia

Answer

Cystic fibrosis

Answer

Phenylketonuria

Answer

Alpha-1 antitrypsin deficiency

Question 2

Edwards syndrome is associated with which chromosomal abnormality?

Accepted Answer

Trisomy 18

Answer

Trisomy 21

Answer

Trisomy 13

Answer

5p deletion

Question 3

Adrenomyeloneuropathy, a variant of adrenoleukodystrophy which manifests as adrenal insufficiency beginning in childhood and later develops into a progressive spastic paraparesis, is transmitted as:

Accepted Answer

X-linked disorder

Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

Sporadic

Question 4

Fredrich's ataxia is caused by which type of mutation?

Accepted Answer

Expanded trinucleotide repeat

Answer

Point mutation

Answer

Missense mutation

Answer

Inversion

Question 5

Non-frameshift mutation of the dystrophin gene causes which of the following conditions?

Accepted Answer

Becker's Muscular Dystrophy

Answer

Duchenne Muscular Dystrophy

Answer

Myotonic Dystrophy

Answer

Limb Girdle Dystrophy

Question 6

Classic form of Alport syndrome is inherited as:

Accepted Answer

X-linked

Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

Sporadic

Question 7

Which of the following statements about Hemochromatosis is true?

Accepted Answer

Inherited as an autosomal recessive disorder

Answer

Phlebotomy is curative

Answer

More common in females

Answer

Shows complete penetrance

Question 8

Which one of the following neurological conditions is not inherited in an autosomal dominant pattern?

Accepted Answer

Friedreich's ataxia

Answer

Neurofibromatosis

Answer

Marfan's syndrome

Answer

Bloom syndrome

Question 9

Mental retardation is NOT a feature of which of the following mucopolysaccharidoses?

Accepted Answer

Sanfilippo syndrome (MPS III)

Answer

Hurler syndrome (MPS I)

Answer

Hunter syndrome (MPS II)

Answer

Morquio syndrome (MPS IV)

Question 10

Duchenne's muscular dystrophy is inherited in which pattern?

Accepted Answer

X-linked recessive

Answer

X-linked dominant

Answer

Autosomal dominant

Answer

Autosomal recessive

Genetics and Disease — MCQs

Genetics and Disease — MCQs

On this page

Practice by Chapter

Want unlimited practice?