Genetics and Disease Practice Questions

Q: McArdle's syndrome is due to which of the following deficiencies?

Deficiency of glucose-6-phosphatase. Detailed Analysis: McArdle’s disease (GSD Type V) is an autosomal recessive metabolic disorder characterized by the **absence of muscle phosphorylase** (myophosphorylase) [1]. This enzyme is essential for glycogenolysis in skeletal muscle; its deficiency prevents the breakdown of muscle glycogen into glucose-1-phosphate, leading to an energy crisis during the initial stages of exercise [1]. **Analysis of Options:** * **Option B (Correct):** McArdle’s disease is specifically caused by a deficiency of **muscle phosphorylase**. This leads to exercise intolerance, muscle cramps, and myoglobinuria [2]. * **Option A (Incorrect):** Deficiency of **glucose-6-phosphatase** causes **Von Gierke’s disease (GSD Type I)**, characterized by severe fasting hypoglycemia, hepatomegaly, and hyperuricemia [1]. * **Option C (Incorrect):** Deficiency of **liver phosphorylase** causes **Hers disease (GSD Type VI)**, which presents with hepatomegaly and mild hypoglycemia. * **Option D (Incorrect):** Deficiency of **liver phosphorylase kinase** causes **GSD Type IX**, which is clinically similar to Hers disease. **Clinical Pearls for NEET-PG:** 1. **Second Wind Phenomenon:** A hallmark of McArdle’s where patients experience relief from fatigue/cramps after a few minutes of exercise as the body switches to using free fatty acids and blood glucose. 2. **Ischemic Forearm Exercise Test:** Classically shows a **failure of blood lactate to rise** with a concomitant rise in ammonia levels. 3. **Burgundy-colored urine:** Post-exercise myoglobinuria can lead to acute renal failure. 4. **Biopsy:** Shows subsarcolemmal deposits of glycogen.

Q: Which of the following conditions is NOT caused by the overexpression of a trinucleotide repeat?

Alzheimer's disease. **Explanation:** The correct answer is **Alzheimer’s disease**. This condition is a neurodegenerative disorder primarily associated with the accumulation of amyloid-beta plaques and tau tangles [1]. Its genetic basis involves mutations in the **APP, PSEN1, and PSEN2** genes (early-onset) or the **APOE-ε4** allele (late-onset), rather than trinucleotide repeat expansions. **Analysis of Options:** * **Fragile X Syndrome:** Caused by a **CGG** repeat expansion in the *FMR1* gene. It is the most common inherited cause of intellectual disability. * **Huntington Disease:** An autosomal dominant disorder caused by **CAG** repeats in the *HTT* gene on chromosome 4 [2]. It exhibits "anticipation," where the disease manifests earlier in successive generations. * **Spinocerebellar Ataxia (SCA) Type 2:** Part of a group of autosomal dominant ataxias caused by **CAG** repeats (polyglutamine diseases) affecting the *ATXN2* gene [2]. **NEET-PG High-Yield Pearls:** 1. **Anticipation:** This phenomenon (earlier onset/increased severity in offspring) is a hallmark of trinucleotide repeat disorders due to further expansion during gametogenesis. 2. **Repeat Locations:** * **CAG (Polyglutamine):** Huntington’s, SCA, Spinal Bulbar Muscular Ataxia (Kennedy disease). * **CGG:** Fragile X (Non-coding region). * **GAA:** Friedreich’s Ataxia (Intronic). * **CTG:** Myotonic Dystrophy. 3. **Alzheimer’s Association:** Down Syndrome patients have an increased risk of Alzheimer’s because the *APP* gene is located on **Chromosome 21**.

Q: If both parents are sickle cell anemia patients, what is the likelihood of their offspring having the disease?

100%. **Explanation:** **1. Why the Correct Answer is Right:** Sickle Cell Anemia (SCA) is an **autosomal recessive** disorder caused by a point mutation in the HBB gene on chromosome 11. For an individual to manifest the disease (SCA), they must possess two copies of the mutated hemoglobin S (HbS) allele (genotype: **ss**) [1]. In this scenario, both parents are patients (not just carriers), meaning both have the genotype **ss**. According to Mendelian inheritance, a cross between two homozygous recessive parents (**ss × ss**) will result in offspring that are all **ss**. Therefore, there is a **100% probability** that every child will inherit the disease. **2. Why the Incorrect Options are Wrong:** * **Option A (10%):** This value does not correspond to any standard Mendelian inheritance pattern for a single-gene disorder. * **Option B (25%):** This is the risk of having an affected child when **both parents are carriers** (Sickle Cell Trait, genotype **As**). * **Option C (50%):** This is the risk when **one parent is a patient (ss)** and the **other is a carrier (As)**. **3. NEET-PG Clinical Pearls & High-Yield Facts:** * **Molecular Basis:** Glutamic acid is replaced by **Valine** at the 6th position of the beta-globin chain. * **Sickling Trigger:** Occurs under conditions of hypoxia, acidosis, and dehydration. * **Protective Effect:** Heterozygotes (Sickle Cell Trait) have a selective advantage against *Plasmodium falciparum* malaria. * **Diagnosis:** **High-Performance Liquid Chromatography (HPLC)** is the gold standard; Solubility tests and peripheral smears (sickle cells, Howell-Jolly bodies) are screening tools [1]. * **Management:** Hydroxyurea is used to increase **HbF** levels, which inhibits the polymerization of HbS [1].

Q: In Von Hippel-Lindau Syndrome, retinal vascular tumors are often associated with intracranial hemangioblastomas. Which one of the following regions is associated with such vascular abnormalities in this syndrome?

Cerebellum. **Explanation:** **Von Hippel-Lindau (VHL) Syndrome** is an autosomal dominant multisystem disorder caused by a mutation in the **VHL gene on chromosome 3p25**. This gene normally acts as a tumor suppressor by degrading Hypoxia-Inducible Factor (HIF). Its loss leads to the overproduction of angiogenic factors like VEGF, resulting in highly vascular tumors. **Why the Correct Answer is Right:** The hallmark CNS lesion in VHL is the **hemangioblastoma**. These are benign but highly vascular tumors that most commonly occur in the **Cerebellum (60-80%)**, followed by the spinal cord and brainstem. In this question, the association of retinal angiomas (von Hippel tumors) with cerebellar hemangioblastomas (Lindau tumors) defines the classic presentation of the syndrome. **Why the Incorrect Options are Wrong:** * **Optic radiation, Optic tract, and Pulvinar:** While VHL affects the visual system via retinal hemangioblastomas, it does not typically cause vascular tumors in the retro-chiasmal pathways (tracts/radiations) or the thalamic nuclei (pulvinar). Hemangioblastomas in VHL have a predilection for the **infratentorial compartment** (posterior fossa) rather than the supratentorial white matter or deep gray matter. **High-Yield Clinical Pearls for NEET-PG:** * **VHL Gene:** Chromosome **3**. * **Classic Triad:** Retinal hemangioblastomas, Cerebellar hemangioblastomas, and Renal Cell Carcinoma (RCC). * **Associated Findings:** Pheochromocytoma (Type 2 VHL), Pancreatic cysts/NETs, and Endolymphatic sac tumors (causing hearing loss). * **RCC Type:** Clear cell variant (often bilateral and multifocal). * **Most common cause of death:** Renal Cell Carcinoma or complications from CNS hemangioblastomas.

Q: Which of the following is NOT a characteristic of Xeroderma Pigmentosum?

It is an autosomal recessive disorder.. The question asks for the statement that is **NOT** a characteristic of Xeroderma Pigmentosum (XP). However, based on medical facts, **Option A is actually a true characteristic** of the disease. In the context of this question, there appears to be a technical error in the provided key, as all four options (A, B, C, and D) are scientifically correct descriptions of XP. ### **Medical Explanation** 1. **Why Option A is a characteristic:** Xeroderma Pigmentosum is a classic **autosomal recessive** genetic disorder [1]. It occurs when a child inherits two mutated copies of the XP genes (XPA through XPG). 2. **Why Option B is a characteristic:** The fundamental pathology is a **defect in Nucleotide Excision Repair (NER)** [1]. This system is responsible for "cutting out" DNA segments damaged by environmental factors. 3. **Why Option C is a characteristic:** Due to the inability to repair DNA, patients have a >1000-fold increased risk of cutaneous malignancies, including **Squamous Cell Carcinoma (SCC)**, Basal Cell Carcinoma (BCC), and Melanoma. 4. **Why Option D is a characteristic:** UV radiation (specifically UV-B) causes the formation of **pyrimidine dimers (thymine dimers)**. In healthy individuals, NER fixes these; in XP patients, they persist, leading to mutations and carcinogenesis. ### **High-Yield Clinical Pearls for NEET-PG** * **Early Sign:** Severe "sunburn" after minimal sun exposure and extensive freckling (lentigines) before age 2. * **Neurological Involvement:** About 20-30% of patients (e.g., De Sanctis-Cacchione syndrome) show progressive neurodegeneration and sensorineural deafness. * **Ocular Findings:** Photophobia, keratitis, and corneal opacification are common. * **Management:** Strict UV protection (sunscreen, protective clothing) and regular dermatological surveillance.

Q: In a family, the father has widely spaced eyes, increased facial hair, and deafness. One of the three children has deafness with similar facial features. The mother is normal. Which one of the following is the most likely pattern of inheritance in this case?

Autosomal dominant. **Explanation:** The clinical presentation described—widely spaced eyes (telecanthus), synophrys (increased facial hair/unibrow), and sensorineural deafness—is characteristic of **Waardenburg Syndrome**. **1. Why Autosomal Dominant (AD) is correct:** In this scenario, the condition is transmitted directly from an affected father to his child. This represents **vertical transmission** (seen in every generation). Since the mother is normal and the trait appears in the offspring, it indicates that a single copy of the mutant allele from the father is sufficient to cause the phenotype. This is the hallmark of Autosomal Dominant inheritance. **2. Why other options are incorrect:** * **Autosomal Recessive (AR):** This typically presents with **horizontal transmission** (skipped generations). For a child to be affected, both parents must usually be carriers. If the mother is "normal" (not a carrier), an AR condition would not manifest in the child. * **X-linked Dominant (XLD):** While an affected father can pass an XLD trait to his daughters, he **cannot** pass it to his sons (as he gives them a Y chromosome). The question mentions "one of three children" without specifying gender; however, AD is the more common and classic fit for Waardenburg Syndrome (Type 1 and 2). * **X-linked Recessive (XLR):** An affected father would pass the gene to all daughters (making them carriers) but none of his children would typically be affected unless the mother was also a carrier. **Clinical Pearls for NEET-PG:** * **Waardenburg Syndrome:** Look for "White forelock" (poliosis), heterochromia iridis (different colored eyes), and sensorineural hearing loss. * **High-Yield Rule:** Vertical transmission + Male-to-Male transmission = **Autosomal Dominant**. * **Mnemonic:** Most structural protein defects are AD; most enzyme deficiencies are AR.

Q: A teenage boy, who was previously raised as a girl, presents with primary amenorrhea and lack of secondary sexual characteristics. On examination, he has tall stature, small testes, and gynecomastia. Which of the following is the most likely genotype?

47,XXY. ***Correct: 47,XXY (Klinefelter Syndrome)*** - This patient presents with **classic features of Klinefelter syndrome**: tall stature, small firm testes, gynecomastia, and hypogonadism [1]. - The **47,XXY karyotype** results from meiotic nondisjunction leading to an extra X chromosome. - **Hypogonadism** causes decreased testosterone, leading to lack of secondary sexual characteristics and increased FSH/LH [1]. - Patients typically have **eunuchoid body proportions** (tall stature with long limbs) due to delayed epiphyseal closure [1]. - The presence of **gynecomastia** is due to relative estrogen excess compared to testosterone [1]. - Primary amenorrhea mentioned here likely refers to the lack of pubertal development (developmental delay). *Incorrect: 47,XYY (Supermale Syndrome)* - These individuals are **tall males with normal virilization** and normal-sized testes - No gynecomastia or hypogonadism - Often associated with learning difficulties but normal sexual development *Incorrect: 45,X (Turner Syndrome)* - Presents in **phenotypic females** with **short stature** (not tall) [2]. - Features include webbed neck, shield chest, coarctation of aorta - Primary amenorrhea present but patient would be raised as female throughout - Does not explain male phenotype or gynecomastia in this case *Incorrect: 46,XX (Normal Female Karyotype)* - Normal female karyotype would not explain **male phenotype** with testes - Does not account for gynecomastia or the clinical presentation described

Q: A mutation in the SOD1 gene is most commonly associated with which of the following conditions?

Amyotrophic lateral sclerosis (ALS). ***Amyotrophic lateral sclerosis (ALS)*** - **SOD1 (Superoxide dismutase 1)** gene mutations are responsible for approximately **20% of familial ALS** cases and 1-2% of sporadic cases - SOD1 enzyme normally protects cells from oxidative damage by converting superoxide radicals to hydrogen peroxide - Mutations lead to **toxic gain of function** causing motor neuron degeneration, affecting both upper and lower motor neurons [1] - Clinical features include progressive muscle weakness, fasciculations, spasticity, and bulbar symptoms [1] - This is one of the **most well-established genetic associations** in neurodegenerative disease *Parkinson's disease* - Associated with mutations in **SNCA (α-synuclein), LRRK2, and Parkin** genes, not SOD1 - Characterized by dopaminergic neuron loss in substantia nigra - Presents with bradykinesia, rigidity, resting tremor, and postural instability *Multiple sclerosis* - An **autoimmune demyelinating disease** with complex genetic susceptibility involving HLA-DRB1 and other immune-related genes - Not linked to SOD1 mutations - Presents with relapsing-remitting neurological symptoms and white matter lesions *Huntington's disease* - Caused by **CAG trinucleotide repeat expansion** in the huntingtin (HTT) gene on chromosome 4 - Autosomal dominant inheritance with anticipation - Presents with chorea, cognitive decline, and psychiatric symptoms

Q: Which of the following genetic mutations is most commonly associated with familial cases of Amyotrophic Lateral Sclerosis (ALS)?

SOD1 gene mutation. ***SOD1 gene mutation***- Mutations in the **Superoxide Dismutase 1 (SOD1)** gene are historically significant and account for approximately 15–20% of all familial ALS cases.- The SOD1 protein is located in the cytoplasm and mitochondria, and mutations lead to toxic misfolding and aggregation, resulting in **motor neuron death**.*CFTR gene mutation*- The **CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)** gene mutation is critically linked to the development of **Cystic Fibrosis**, a severe disorder of exocrine glands.- This mutation primarily affects chloride ion transport across epithelia, leading to highly viscous secretions, particularly in the airways and pancreas, not motor neuron disease.*HTT gene mutation*- Mutations involving the **HTT (Huntingtin)** gene, specifically expanded **CAG trinucleotide repeats**, cause **Huntington's disease**.- Huntington’s disease is characterized by progressive degeneration of the **striatum** and cortex, leading to movement abnormalities (*chorea*), cognitive decline, and psychiatric symptoms, distinct from ALS.*FMR1 gene mutation*- The **FMR1 (Fragile X Messenger Ribonucleoprotein 1)** gene is responsible for **Fragile X syndrome**, the most common inherited cause of intellectual disability.- The mutation involves expansion of the **CGG trinucleotide repeat**, typically leading to transcriptional silencing and symptoms like macroorchidism and behavioral issues, not primary motor neuron degeneration.

Question 1

McArdle's syndrome is due to which of the following deficiencies?

Accepted Answer

Deficiency of glucose-6-phosphatase

Answer

Absence of muscle phosphorylase

Answer

Deficiency of liver phosphorylase

Answer

Deficiency of liver phosphorylase kinase

Question 2

Which of the following conditions is NOT caused by the overexpression of a trinucleotide repeat?

Accepted Answer

Alzheimer's disease

Answer

Fragile X syndrome

Answer

Huntington disease

Answer

Spinocerebellar ataxia Type 2

Question 3

If both parents are sickle cell anemia patients, what is the likelihood of their offspring having the disease?

Accepted Answer

100%

Answer

10%

Answer

25%

Answer

50%

Question 4

In Von Hippel-Lindau Syndrome, retinal vascular tumors are often associated with intracranial hemangioblastomas. Which one of the following regions is associated with such vascular abnormalities in this syndrome?

Accepted Answer

Cerebellum

Answer

Optic radiation

Answer

Optic tract

Answer

Pulvinar

Question 5

Which of the following is NOT a characteristic of Xeroderma Pigmentosum?

Accepted Answer

It is an autosomal recessive disorder.

Answer

It is caused by defective DNA repair.

Answer

It is associated with an increased risk of squamous cell carcinoma.

Answer

Exposure to ultraviolet radiation can lead to the formation of thymine dimers.

Question 6

In a family, the father has widely spaced eyes, increased facial hair, and deafness. One of the three children has deafness with similar facial features. The mother is normal. Which one of the following is the most likely pattern of inheritance in this case?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Answer

X-linked recessive

Question 7

A teenage boy, who was previously raised as a girl, presents with primary amenorrhea and lack of secondary sexual characteristics. On examination, he has tall stature, small testes, and gynecomastia. Which of the following is the most likely genotype?

Accepted Answer

47,XXY

Answer

47,XYY

Answer

45,X

Answer

46,XX

Question 8

A mutation in the SOD1 gene is most commonly associated with which of the following conditions?

Accepted Answer

Amyotrophic lateral sclerosis (ALS)

Answer

Parkinson's disease

Answer

Multiple sclerosis

Answer

Huntington's disease

Question 9

A 15-year-old boy presents with tremors, difficulty in speech, and behavioral changes. On examination, he has hepatomegaly and a golden-brown ring at the limbus of the cornea (Kayser-Fleischer ring). Wilson's disease is suspected. Which of the following is the best investigation to support the diagnosis?

Accepted Answer

Liver biopsy for copper estimation

Answer

Serum ceruloplasmin

Answer

Copper excretion in urine

Answer

Serum copper

Question 10

Which of the following genetic mutations is most commonly associated with familial cases of Amyotrophic Lateral Sclerosis (ALS)?

Accepted Answer

SOD1 gene mutation

Answer

HTT gene mutation

Answer

CFTR gene mutation

Answer

FMR1 gene mutation

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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