Molecular Pathology Practice Questions

Q: Steroid-resistant nephrotic syndrome is associated with mutations in which gene?

NPHS2. **Explanation:** The correct answer is **A. NPHS2**. **1. Why NPHS2 is correct:** Steroid-resistant nephrotic syndrome (SRNS) is frequently caused by genetic mutations affecting the structural integrity of the glomerular filtration barrier [1]. The **NPHS2 gene** encodes **Podocin**, a critical integral membrane protein localized to the slit diaphragm of podocytes [1]. Mutations in NPHS2 lead to autosomal recessive SRNS, typically manifesting as Focal Segmental Glomerulosclerosis (FSGS). Unlike minimal change disease, these genetic forms do not respond to corticosteroid therapy because the defect is structural rather than immunological [1]. **2. Why the other options are incorrect:** * **HOX11 (TLX1):** This is a homeobox gene primarily associated with T-cell acute lymphoblastic leukemia (T-ALL) and spleen development, not renal filtration. * **PAX:** The PAX gene family (e.g., PAX2, PAX8) is crucial for kidney development (nephrogenesis). Mutations in PAX2 are associated with Renal-Coloboma Syndrome, characterized by optic nerve coloboma and renal hypoplasia, but not specifically SRNS. * **ACE:** The Angiotensin-Converting Enzyme gene is studied for its role in hypertension and the progression of chronic kidney disease, but it is not the primary causative mutation for steroid-resistant nephrotic syndrome. **High-Yield Clinical Pearls for NEET-PG:** * **NPHS1:** Encodes **Nephrin**. Mutations cause Finnish-type congenital nephrotic syndrome (autosomal recessive). * **NPHS2:** Encodes **Podocin**. Associated with childhood-onset SRNS and FSGS [1]. * **ACTN4:** Encodes ̡-actinin-4; mutations cause an autosomal dominant form of FSGS [1]. * **WT1:** Mutations can lead to Denys-Drash syndrome (nephropathy, Wilms tumor, and intersex disorders). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 921-928.

Q: The gene for Wilms tumor is located on which chromosome?

Chromosome 11. **Explanation:** **1. Why Chromosome 11 is Correct:** Wilms tumor (Nephroblastoma) is the most common primary renal tumor of childhood. Its pathogenesis is strongly linked to the **WT1 (Wilms Tumor 1) gene**, which is located on **Chromosome 11p13** [1]. This gene is essential for normal renal and gonadal development. Mutations or deletions in this region are associated with sporadic Wilms tumor and syndromic forms like **WAGR syndrome** (Wilms tumor, Aniridia, Genitourinary anomalies, and mental Retardation) [1]. Additionally, the **WT2 gene** locus is located on **Chromosome 11p15.5**, associated with **Beckwith-Wiedemann Syndrome**. **2. Analysis of Incorrect Options:** * **Chromosome 1:** While many cancers have secondary changes here, it is not the primary locus for Wilms tumor. However, 1p deletions are sometimes seen as a poor prognostic marker in Wilms. * **Chromosome 10:** This is the location of the **PTEN gene** (Cowden syndrome) and the **RET proto-oncogene** (MEN 2A/2B and Medullary Thyroid Carcinoma). * **Chromosome 12:** Associated with genes like **KRAS** and certain sarcomas (e.g., Clear cell sarcoma of the kidney), but not the classic Wilms tumor gene. **3. High-Yield Clinical Pearls for NEET-PG:** * **Histology:** Characterized by a **triphasic pattern** (Blastema, Stroma, and Epithelium). * **Denys-Drash Syndrome:** Associated with WT1 mutations, characterized by gonadal dysgenesis and early-onset nephropathy. * **Beckwith-Wiedemann Syndrome (BWS):** Linked to the WT2 locus (11p15.5); features include macroglossia, organomegaly, and hemihypertrophy. * **Prognosis:** The presence of **anaplasia** (TP53 mutation) is the most important histological predictor of poor prognosis. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 487-488.

Q: All of the following are true about dyskeratosis congenita, EXCEPT:

Cutaneous depigmentation. ### Explanation **Dyskeratosis Congenita (DKC)** is a rare inherited bone marrow failure syndrome characterized by the classic **clinical triad**: 1. **Nail dystrophy** (ridged, split, or absent nails) 2. **Oral leukoplakia** (white patches on the tongue/mucosa) 3. **Reticular skin hyperpigmentation** (typically in a "lace-like" pattern on the neck and chest) **Why Option A is the Correct Answer:** The cutaneous manifestation of DKC is **hyperpigmentation**, not depigmentation. The skin changes usually appear in the first decade of life and are characterized by a dusky, reticular (net-like) pattern of increased melanin deposition. **Analysis of Other Options:** * **Option B (Leukoplakia):** This is a hallmark of the classic triad. It carries a high risk of malignant transformation into squamous cell carcinoma. * **Option C (Nail Dystrophy):** This is often the earliest sign of the triad, appearing in early childhood. * **Option D (Shortened telomere length):** DKC is fundamentally a **"telomeropathy."** It is caused by mutations in genes responsible for telomere maintenance (e.g., *DKC1, TERC, TERT*). Measuring telomere length in peripheral blood leukocytes via Flow-FISH is the gold-standard diagnostic test. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** Most commonly X-linked recessive (*DKC1* gene encoding **dyskerin**), but autosomal dominant and recessive forms exist. * **Primary Cause of Death:** Bone marrow failure (aplastic anemia) occurs in ~80% of patients. * **Cancer Risk:** Significant predisposition to Head and Neck Squamous Cell Carcinoma (HNSCC) and Myelodysplastic Syndrome (MDS). * **Hoyeraal-Hreidarsson Syndrome:** A severe variant of DKC characterized by cerebellar hypoplasia and immunodeficiency.

Q: Angelman syndrome is caused by:

Maternal imprinting. **Explanation:** Angelman syndrome is a classic example of **Genomic Imprinting**, an epigenetic process where certain genes are expressed in a parent-of-origin-specific manner [1]. **1. Why Maternal Imprinting is Correct:** In normal individuals, the **UBE3A gene** on chromosome 15 (15q11-q13) is active only on the maternal chromosome, while the paternal copy is silenced (imprinted). Angelman syndrome occurs when the **maternal** contribution is lost—either through a deletion of the maternal 15q11-q13 region (70% of cases), paternal uniparental disomy (two copies from the father), or imprinting defects [1]. Because the paternal gene is already silenced, the loss of the functional maternal gene leads to a total lack of UBE3A expression in the brain. **2. Why Other Options are Incorrect:** * **Paternal Imprinting:** This refers to the silencing of the paternal allele. If the **paternal** contribution is lost (and the maternal copy is silenced), it results in **Prader-Willi Syndrome**, not Angelman [1]. * **Both/None:** These are incorrect as the syndromes are distinct clinical entities based on which parental allele is defective [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic:** **M**aternal = **A**ngelman (**M**appy **A**ngel); **P**aternal = **P**rader-Willi (**P**opular **P**rader). * **Angelman Presentation:** "Happy Puppet" syndrome—characterized by inappropriate laughter, seizures, ataxia, and severe intellectual disability [1]. * **Prader-Willi Presentation:** Hyperphagia (obesity), hypogonadism, and hypotonia [1]. * **Diagnosis:** Fluorescence in situ hybridization (FISH) or methylation-specific PCR [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 181-182.

Question 1

Which of the following is a pro-apoptotic factor?

Accepted Answer

Bax

Answer

Bcl-2

Answer

Bcl-xL

Answer

Mcl-1

Question 2

In Vitamin-A deficiency, cancerous lesions occur due to which cellular adaptation?

Accepted Answer

Metaplasia

Answer

Dysplasia

Answer

Aplasia

Answer

Hyperplasia

Question 3

Steroid-resistant nephrotic syndrome is associated with mutations in which gene?

Accepted Answer

NPHS2

Answer

HOX11

Answer

PAX

Answer

ACE

Question 4

Which of the following chromosomal abnormalities will exhibit two Barr bodies?

Accepted Answer

47, XXX

Answer

47, XXY

Answer

45, X0

Answer

46, XY

Question 5

A 56-year-old chronic smoker presents with a mass in the bronchus that was resected. What is the most useful immunohistochemical marker for making a definitive diagnosis?

Accepted Answer

Cytokeratin

Answer

Vimentin

Answer

Epithelial membrane antigen

Answer

Leukocyte common antigen

Question 6

The gene for Wilms tumor is located on which chromosome?

Accepted Answer

Chromosome 11

Answer

Chromosome 1

Answer

Chromosome 10

Answer

Chromosome 12

Question 7

All of the following are true about dyskeratosis congenita, EXCEPT:

Accepted Answer

Cutaneous depigmentation

Answer

Leukoplakia

Answer

Nail dystrophy

Answer

Shortened telomere length in leukocytes

Question 8

Cat eye syndrome is a chromosomal abnormality characterized by which of the following?

Accepted Answer

Trisomy 22

Answer

Trisomy 18

Answer

Trisomy 13

Answer

Trisomy 21

Question 9

Angelman syndrome is caused by:

Accepted Answer

Maternal imprinting

Answer

Paternal imprinting

Answer

Both of the above

Answer

None of the above

Question 10

Which of the following tests is not used for the detection of specific aneuploidy?

Accepted Answer

Microarray

Answer

FISH

Answer

None

Answer

QF-PCR

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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