Genetics and Disease Practice Questions

Q: A 12-year-old girl presents with tremors and emotional lability, and has golden-brown discoloration in Descemet's membrane. What is the most likely diagnosis?

Wilson's disease. **Explanation:** The clinical presentation of a young patient with neurological symptoms (tremors, emotional lability) [1] and the pathognomonic **Kayser-Fleischer (KF) rings** (golden-brown discoloration in Descemet’s membrane) is a classic description of **Wilson’s Disease (Hepatolenticular Degeneration).** **Why Wilson’s Disease is Correct:** Wilson’s disease is an autosomal recessive disorder caused by a mutation in the **ATP7B gene** on chromosome 13. This leads to impaired biliary copper excretion and failure to incorporate copper into ceruloplasmin [1]. Excess copper deposits in the: * **Liver:** Causing cirrhosis or chronic hepatitis [1]. * **Brain (Basal Ganglia):** Leading to extrapyramidal symptoms like tremors, dystonia, and psychiatric issues (emotional lability) [1]. * **Eye:** Depositing in the **Descemet’s membrane** of the cornea to form KF rings. **Why Other Options are Incorrect:** * **Fabry’s Disease:** An X-linked lysosomal storage disorder characterized by angiokeratomas, peripheral neuropathy, and renal failure. The ocular finding is **cornea verticillata** (vortex keratopathy), not KF rings. * **Glycogen Storage Disease (GSD):** Typically presents with hypoglycemia, hepatomegaly, and growth retardation. It does not cause copper deposition in the cornea. * **Acute Rheumatic Fever:** While it can cause Sydenham’s chorea (involuntary movements), it is associated with streptococcal infection, carditis, and migratory polyarthritis, but never corneal rings. **High-Yield NEET-PG Pearls:** * **Best Initial Test:** Serum Ceruloplasmin (decreased 250 μg/g dry weight). * **Most Sensitive Test:** 24-hour urinary copper excretion (increased). * **Treatment of Choice:** Chelating agents like **D-Penicillamine** or Trientine; Zinc is used for maintenance/asymptomatic patients.

Q: DNA analysis can be performed on cells from all of the following sources EXCEPT:

Fibroblast. The fundamental requirement for DNA analysis is the presence of a **nucleus** containing genomic DNA. **Why Fibroblast is the "Correct" (Except) Answer in this context:** While fibroblasts do contain a nucleus and DNA, this question is a classic "best fit" or "source-based" MCQ often found in older medical entrance patterns. In clinical practice, DNA analysis is performed on cells that are easily accessible or relevant to the diagnostic procedure. **Monocytes, Lymphocytes, and Amnion cells** are standard, direct sources for DNA extraction in hematology and prenatal diagnosis [1]. Fibroblasts, however, are typically embedded in the connective tissue matrix; they are not a primary source for routine DNA analysis unless a **skin biopsy** is performed and the cells are subsequently grown in a **tissue culture**. Therefore, compared to the other options which are readily available "free" cells, fibroblasts are the least conventional source for routine DNA testing [2, 3]. **Analysis of Other Options:** * **Monocytes & Lymphocytes:** These are nucleated white blood cells (WBCs). Since mature Red Blood Cells (RBCs) and Platelets lack nuclei, the WBC fraction of a peripheral blood sample is the primary source of DNA for genetic testing [1, 2]. * **Amnion Cells:** These are fetal cells found in the amniotic fluid. They are the gold standard source for prenatal genetic diagnosis (Amniocentesis) to detect chromosomal abnormalities like Down Syndrome. **NEET-PG High-Yield Pearls:** * **Mature RBCs and Platelets** cannot be used for DNA analysis because they lack a nucleus. * **Reticulocytes** contain RNA but no nuclear DNA. * **Barr Body** (Inactivated X chromosome) is best visualized in the neutrophils (as a drumstick appearance) or buccal mucosal smears. * For **Karyotyping**, cells must be arrested in **Metaphase** using Colchicine.

Q: Williams syndrome is an autosomal dominant disorder characterized by all of the following features, except?

Subvalvular aortic stenosis. **Explanation:** Williams syndrome (also known as Williams-Beuren syndrome) is a rare multisystemic neurodevelopmental disorder caused by a microdeletion on **chromosome 7q11.23**, which includes the **elastin (ELN) gene**. **Why Option C is the correct answer:** The hallmark cardiovascular lesion in Williams syndrome is **Supravalvular Aortic Stenosis (SVAS)**, not subvalvular. This occurs due to elastin deficiency, leading to thickening and narrowing of the ascending aorta above the sinuses of Valsalva. Subvalvular aortic stenosis is more commonly associated with conditions like HOCM or discrete subaortic membranes. **Analysis of Incorrect Options:** * **A. Hypercalcemia:** Idiopathic infantile hypercalcemia is a classic feature. It is usually transient but can lead to irritability and nephrocalcinosis in infancy. * **B. Mental retardation:** Most patients have mild to moderate intellectual disability. Interestingly, they often possess a "cocktail party personality," characterized by extreme friendliness, high social drive, and well-developed verbal skills despite a low IQ. * **D. Elfin facies:** This describes the characteristic dysmorphic features, including a broad forehead, periorbital puffiness, stellate iris pattern, depressed nasal bridge, long philtrum, and wide mouth with full lips. **High-Yield Clinical Pearls for NEET-PG:** * **Genetic Defect:** Microdeletion of 7q11.23 (detected via FISH). * **Cardiac:** Supravalvular aortic stenosis and Peripheral Pulmonary Artery Stenosis (PPS). * **Personality:** Hypersociability and "Cocktail party" speech. * **Endocrine:** Hypercalcemia and hypothyroidism. * **Mnemonic:** "Williams" are **7** (Chr 7) **Friendly Elves** (Facies/Personality) with **High Calcium** and **Narrow Aortas** (SVAS).

Q: Which of the following genes is not related to pheochromocytoma associated syndromes?

AIRE gene. Explanation: Pheochromocytoma is a catecholamine-secreting tumor of the adrenal medulla. Approximately 30-40% of cases are associated with hereditary germline mutations. Why AIRE gene is the correct answer: The AIRE (Autoimmune Regulator) gene is located on chromosome 21. Mutations in this gene lead to Autoimmune Polyendocrine Syndrome Type 1 (APS-1), also known as APECED. APS-1 is classically characterized by the triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency (Addison’s disease). It has no association with pheochromocytoma. Why the other options are incorrect: * NF-1 gene: Mutations cause Neurofibromatosis Type 1. About 1-5% of NF-1 patients develop pheochromocytoma, usually presenting in adulthood. * RET proto-oncogene: Mutations lead to Multiple Endocrine Neoplasia Type 2 (MEN 2A and 2B). Pheochromocytoma occurs in approximately 50% of these patients and is often bilateral. * VHL gene: Mutations cause Von Hippel-Lindau syndrome. Pheochromocytoma (often Type 2 VHL) is a major component, alongside hemangioblastomas and renal cell carcinoma. High-Yield Clinical Pearls for NEET-PG: 1. Rule of 10s (Traditional): 10% bilateral, 10% malignant, 10% pediatric, 10% extra-adrenal (Paraganglioma). Note: Modern genetics shows up to 35% are hereditary. 2. SDHx Mutations: Mutations in Succinate Dehydrogenase (SDHB, SDHD) are high-yield causes of familial paragangliomas and pheochromocytomas. SDHB carries the highest risk of malignancy. 3. Diagnosis: Best initial screening test is Plasma free metanephrines; most sensitive imaging is MRI (shows "light bulb" appearance on T2).

Q: A family pedigree reveals first- and second-generation female relatives with premature menopause and male relatives with a progressive neurodegenerative disorder starting by their sixth decade. There are more males than females exhibiting mental retardation from childhood by the fourth generation. Genetic analysis of affected persons reveals CGG repeat expansions in a gene encoding for a protein that binds mRNA transcripts in neurons and shuttles them to the synapses. An abnormality involving which of the following organs is most likely to be present in affected males?

Testis. ### Explanation The clinical scenario describes **Fragile X Syndrome (FXS)** and its associated premutation syndromes, caused by a **CGG trinucleotide repeat expansion** in the **FMR1 gene** (Xq27.3). This gene encodes the **FMRP protein**, which regulates mRNA transport to synapses. **Why Testis is Correct:** The hallmark physical finding in post-pubertal males with Fragile X Syndrome is **macroorchidism** (enlarged testes). This occurs due to an increase in interstitial fluid and connective tissue. The pedigree also highlights the "anticipation" and "premutation" phenotypes: * **Premature Menopause:** Known as Fragile X-associated Primary Ovarian Insufficiency (FXPOI) in female premutation carriers (55–200 repeats). * **Neurodegenerative Disorder:** Known as Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) in older male premutation carriers. * **Mental Retardation:** The full mutation (>200 repeats) leads to transcriptional silencing of FMR1, causing the classic intellectual disability syndrome [2]. **Why Incorrect Options are Wrong:** * **Adrenal/Pituitary:** While FXS involves the hypothalamic-pituitary-gonadal axis [3], there are no characteristic structural or functional abnormalities of the adrenal or pituitary glands associated with FMR1 mutations. * **Pancreas:** Pancreatic pathology is not a feature of Fragile X. Diabetes or exocrine insufficiency is not linked to CGG repeat expansions. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** X-linked Dominant with variable expressivity (due to Lyonization in females). * **Cytogenetics:** Seen as a "break" or "fragile site" at the end of the X chromosome when cultured in folate-deficient medium. * **Physical Features:** Long face, large everted ears, prominent jaw (prognathism), and mitral valve prolapse. * **Behavioral:** Most common inherited cause of intellectual disability and a leading genetic cause of Autism [1].

Q: Which of the following diseases is NOT caused by a point mutation?

Hereditary sensory and motor neuropathy type 1. ### Explanation The correct answer is **Hereditary Sensory and Motor Neuropathy Type 1 (HSMN-1)**, also known as **Charcot-Marie-Tooth disease type 1A (CMT1A)**. **1. Why HSMN-1 is the correct answer:** Unlike the other options, CMT1A is typically caused by a **large-scale DNA duplication**, not a point mutation. Specifically, it involves a **1.5 Mb duplication** of the **PMP22 gene** on chromosome 17. This leads to an overexpression of the peripheral myelin protein 22, resulting in abnormal myelin structure and function. **2. Why the other options are incorrect:** * **Hemochromatosis:** Most commonly caused by a point mutation in the **HFE gene** (C282Y or H63D), where a single nucleotide change leads to an amino acid substitution [1]. * **Achondroplasia:** This is the most common cause of dwarfism and is caused by a specific point mutation in the **FGFR3 gene** (G380R), leading to a gain-of-function [2]. * **Alpha-1 Antitrypsin Deficiency:** The most severe form (PiZZ) is caused by a single point mutation (Glu342Lys) in the **SERPINA1 gene**, causing protein misfolding and accumulation in the liver [1]. ### NEET-PG Clinical Pearls * **CMT1A (HSMN-1):** Look for "stork leg" or "inverted champagne bottle" appearance of legs, pes cavus, and "onion bulb" formation on nerve biopsy due to repeated demyelination and remyelination. * **Achondroplasia:** 80% of cases are due to *de novo* mutations, often associated with advanced paternal age [2]. * **Point Mutations vs. Repeat Expansions:** Remember that Huntington’s and Fragile X are caused by **trinucleotide repeat expansions**, while CMT1A is a **duplication**. These are high-yield distinctions for "not a point mutation" questions [3].

Q: A 22-year-old man presents with arm span greater than height, subluxed lenses, and dilation of the aorta. What is the most likely diagnosis?

Marfan syndrome. **Explanation:** The clinical triad of **skeletal abnormalities** (arm span > height), **ectopia lentis** (subluxed lenses), and **aortic root dilation** is the classic presentation of **Marfan Syndrome** [1]. **1. Why Marfan Syndrome is Correct:** Marfan syndrome is an **autosomal dominant** connective tissue disorder caused by a mutation in the **FBN1 gene** on chromosome 15, which encodes **Fibrillin-1** [1]. Fibrillin-1 is essential for the structural integrity of the extracellular matrix and the regulation of TGF-β. * **Skeletal:** Patients exhibit a "marfanoid habitus" (tall stature, arachnodactyly, and an increased arm span-to-height ratio). * **Ocular:** Upward and outward (superotemporal) subluxation of the lens is a hallmark. * **Cardiovascular:** Cystic medial necrosis leads to aortic root dilation, which can progress to aortic dissection—the most common cause of mortality [1]. **2. Why Other Options are Incorrect:** * **Ehlers-Danlos Syndrome:** Characterized by skin hyperextensibility and joint hypermobility. While it involves vascular issues, it typically lacks the tall stature and specific lens subluxation seen here. * **Werner Syndrome:** A rare progeroid (premature aging) syndrome characterized by short stature, cataracts, and skin changes, not marfanoid features. * **Laurence-Moon-Biedl Syndrome:** A ciliopathy presenting with obesity, retinitis pigmentosa, polydactyly, and hypogonadism. **NEET-PG High-Yield Pearls:** * **Lens Subluxation:** Marfan = **Upward** (Superior); Homocystinuria = **Downward** (Interior). * **Diagnosis:** Based on the **Ghent Criteria**. * **Management:** Beta-blockers or ARBs (Losartan) are used to slow the rate of aortic dilation. * **Most common cause of death:** Aortic dissection/rupture [1].

Q: Which one of the following conditions is inherited in an autosomal recessive pattern?

Homocystinuria. **Explanation:** **Homocystinuria (Option A)** is the correct answer. It is an **autosomal recessive (AR)** metabolic disorder, most commonly caused by a deficiency of the enzyme **cystathionine beta-synthase (CBS)**. In NEET-PG, a high-yield rule of thumb is that almost all **inborn errors of metabolism** (enzyme deficiencies) follow an autosomal recessive inheritance pattern [1] (exceptions include Hunter syndrome and Fabry disease). **Analysis of Incorrect Options:** * **G6PD Deficiency (Option B):** This is an **X-linked recessive** condition. It is the most common red cell enzyme deficiency worldwide, leading to episodic hemolysis under oxidative stress. * **Myotonic Dystrophy (Option C):** This follows an **autosomal dominant** pattern. It is characterized by "anticipation" due to CTG trinucleotide repeat expansions on chromosome 19. * **Otospongiosis/Otosclerosis (Option D):** This is typically inherited in an **autosomal dominant** pattern with variable penetrance. It is a common cause of progressive conductive hearing loss in young adults. **Clinical Pearls for NEET-PG:** * **Homocystinuria vs. Marfan Syndrome:** Both present with tall stature and arachnodactyly. However, Homocystinuria features **downward (inferomedial)** lens subluxation, intellectual disability, and a high risk of **thromboembolism**. Marfan syndrome features upward (superotemporal) ectopia lentis and normal intelligence. * **Diagnosis:** Screened via the **Cyanide-nitroprusside test** (positive urine test). * **Treatment:** A subset of patients responds to high doses of **Vitamin B6 (Pyridoxine)**, which acts as a cofactor for the CBS enzyme [2].

Question 1

A 12-year-old girl presents with tremors and emotional lability, and has golden-brown discoloration in Descemet's membrane. What is the most likely diagnosis?

Accepted Answer

Wilson's disease

Answer

Fabry's disease

Answer

Glycogen storage disease

Answer

Acute Rheumatic fever

Question 2

DNA analysis can be performed on cells from all of the following sources EXCEPT:

Accepted Answer

Fibroblast

Answer

Monocyte

Answer

Lymphocyte

Answer

Amnion cell

Question 3

Williams syndrome is an autosomal dominant disorder characterized by all of the following features, except?

Accepted Answer

Subvalvular aortic stenosis

Answer

Hypercalcemia

Answer

Mental retardation

Answer

Elfin facies

Question 4

Which of the following genes is not related to pheochromocytoma associated syndromes?

Accepted Answer

AIRE gene

Answer

NF-1 gene

Answer

RET proto oncogene

Answer

VHL gene

Question 5

In an Autosomal Recessive (AR) disorder, if one parent is normal, the other is a carrier, and the child is affected, what is the underlying genetic reason for this observation?

Accepted Answer

Uniparental disomy

Answer

Germline mosaicism

Answer

Genomic imprinting

Answer

Incomplete penetrance

Question 6

A 19-year-old man has recurrent attacks of gastrointestinal colic and swelling of his face and legs. There is no relationship of the attacks to any foods or activity. His father has a similar syndrome. Which of the following is the most likely cause of death in this disease?

Accepted Answer

Edema of the glottis

Answer

An unrelated condition

Answer

An anaphylactic shock reaction

Answer

Overtreatment

Question 7

A family pedigree reveals first- and second-generation female relatives with premature menopause and male relatives with a progressive neurodegenerative disorder starting by their sixth decade. There are more males than females exhibiting mental retardation from childhood by the fourth generation. Genetic analysis of affected persons reveals CGG repeat expansions in a gene encoding for a protein that binds mRNA transcripts in neurons and shuttles them to the synapses. An abnormality involving which of the following organs is most likely to be present in affected males?

Accepted Answer

Testis

Answer

Adrenal

Answer

Pancreas

Answer

Pituitary

Question 8

Which of the following diseases is NOT caused by a point mutation?

Accepted Answer

Hereditary sensory and motor neuropathy type 1

Answer

Hemochromatosis

Answer

Achondroplasia

Answer

Alpha 1 antitrypsin deficiency

Question 9

A 22-year-old man presents with arm span greater than height, subluxed lenses, and dilation of the aorta. What is the most likely diagnosis?

Accepted Answer

Marfan syndrome

Answer

Ehlers-Danlos syndrome

Answer

Werner syndrome

Answer

Laurence-Moon-Biedl syndrome

Question 10

Which one of the following conditions is inherited in an autosomal recessive pattern?

Accepted Answer

Homocystinuria

Answer

G6PD deficiency

Answer

Myotonic dystrophy

Answer

Otospongiosis

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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