Molecular Pathology Practice Questions

Q: Analyze the provided pedigree chart to identify the underlying genetic disease.

Crouzon syndrome. ***Crouzon syndrome*** - Shows **autosomal dominant inheritance** pattern with multiple generations affected, both sexes involved, and approximately **50% of offspring** affected. - Exhibits **father-to-son transmission**, which is characteristic of autosomal dominant conditions and excludes X-linked inheritance. *Sickle cell anaemia* - Follows **autosomal recessive inheritance** where typically only one generation is affected with unaffected parents having affected children. - Would require **both parents to be carriers** and show a **25% recurrence risk** in offspring, not the pattern seen in the pedigree. *Diabetes insipidus* - Most forms are **acquired** rather than inherited, and when hereditary, usually show **autosomal dominant** or **X-linked recessive** patterns. - **Nephrogenic diabetes insipidus** (X-linked) would show male predominance with no father-to-son transmission, inconsistent with this pedigree. *Hunter syndrome* - Exhibits **X-linked recessive inheritance** with affected males and carrier females, showing a distinctive pattern. - Would demonstrate **no father-to-son transmission** and predominantly affect males through carrier mothers, unlike the pedigree shown.

Q: All of the following are intermediate filaments except?

Cadherin. **Explanation:** The cytoskeleton of a cell consists of three main components: microfilaments (actin), microtubules (tubulin), and **intermediate filaments (IFs)**. Intermediate filaments provide mechanical strength to cells and are categorized into several types based on their tissue distribution. **Why Cadherin is the correct answer:** **Cadherins** are not intermediate filaments; they are **transmembrane cell adhesion molecules**. They play a critical role in cell-cell junctions (like desmosomes and adherens junctions) by mediating calcium-dependent adhesion [1]. While cadherins often link to the cytoskeleton internally, they are structurally distinct from the IF family. **Analysis of incorrect options:** * **Lamin (Option A):** These are Type V intermediate filaments located within the nucleus (nuclear lamina). They provide structural support to the nuclear envelope and regulate DNA replication. * **Vimentin (Option C):** A Type III intermediate filament found in cells of **mesenchymal origin** (e.g., fibroblasts, endothelium, smooth muscle). It is a classic IHC marker for sarcomas. * **Desmin (Option D):** Also a Type III intermediate filament, specifically found in **all types of muscle cells** (skeletal, cardiac, and smooth). It is used as an IHC marker to identify myogenic tumors (e.g., rhabdomyosarcoma). **High-Yield Clinical Pearls for NEET-PG:** * **Cytokeratin:** IF for epithelial cells (Marker for Carcinomas). * **GFAP:** IF for glial cells (Marker for Astrocytomas). * **Neurofilaments:** IF for neurons (Marker for Neuroblastoma/Pheochromocytoma). * **Mallory Hyaline:** These are inclusions of pre-keratin intermediate filaments found in alcoholic liver disease. * **Diagnostic Tip:** If a question asks for a marker of "mesenchymal origin," always look for **Vimentin**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. With Illustrations By, pp. 23-24.

Q: What is the gene involved in GIST?

C-KIT. **Explanation:** **Gastrointestinal Stromal Tumor (GIST)** is the most common mesenchymal tumor of the gastrointestinal tract. The correct answer is **C-KIT** because approximately 85-90% of GISTs are driven by oncogenic gain-of-function mutations in the **c-KIT gene** (which encodes the CD117 receptor tyrosine kinase) [1]. This mutation leads to constitutive activation of the kinase signaling pathway, resulting in uncontrolled cell proliferation [1]. **Analysis of Options:** * **C-KIT (CD117):** This is the hallmark diagnostic marker for GIST. In cases where c-KIT is negative, mutations in **PDGFRA** (Platelet-Derived Growth Factor Receptor Alpha) are often found [1]. * **BRCA-1 & BRCA-2:** These are tumor suppressor genes involved in DNA repair. Mutations are primarily associated with hereditary **Breast and Ovarian Cancer** syndromes, not mesenchymal GI tumors. * **p53:** Known as the "Guardian of the Genome," this is the most commonly mutated gene in human cancers (e.g., Li-Fraumeni syndrome). While it may be involved in the progression of many tumors, it is not the primary driver or diagnostic marker for GIST. **High-Yield Clinical Pearls for NEET-PG:** * **Origin:** GISTs arise from the **Interstitial Cells of Cajal (ICC)**, the pacemakers of the gut [1]. * **Most Common Site:** Stomach (60%), followed by the small intestine. * **Markers:** **CD117** (most specific) and **DOG1** (Discovered on GIST-1). * **Treatment:** The discovery of the c-KIT mutation led to the use of **Imatinib mesylate** (a tyrosine kinase inhibitor), which has revolutionized the prognosis of unresectable or metastatic GIST [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Gastrointestinal Tract, pp. 782-784.

Q: Ring sideroblasts in myelodysplastic syndrome are associated with mutations in which gene?

SF3B1. **Explanation:** **Correct Answer: D. SF3B1** The presence of **ring sideroblasts** (erythroblasts with iron-laden mitochondria encircling the nucleus) is a hallmark of specific subtypes of Myelodysplastic Syndrome (MDS). The **SF3B1** (*Splicing Factor 3b Subunit 1*) gene mutation is highly specific for MDS with ring sideroblasts (MDS-RS). This gene encodes a core component of the RNA splicing machinery (spliceosome) [1]. Mutations lead to aberrant splicing of iron transporters (like *ABCB7*), causing mitochondrial iron accumulation. In the revised WHO/ICC classifications, the presence of an SF3B1 mutation allows for the diagnosis of MDS-RS even if the ring sideroblast count is as low as 5% (compared to the usual 15% threshold). **Incorrect Options:** * **A. ASXL1:** An epigenetic regulator. Mutations are common in MDS and AML but are associated with a **poor prognosis** and do not specifically correlate with ring sideroblasts [1]. * **B. EZH2:** Part of the Polycomb Repressive Complex 2 (PRC2). Mutations are linked to myelofibrosis and MDS but signify an adverse prognosis rather than a specific morphological feature [1]. * **C. TET2:** One of the most common mutations in MDS and Clonal Hematopoiesis of Indeterminate Potential (CHIP). It involves DNA demethylation; while common, it is not specific to the sideroblastic phenotype [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Stain for Ring Sideroblasts:** Perls’ Prussian Blue stain. * **Definition:** ≥5 granules covering at least 1/3rd of the nuclear circumference. * **Prognostic Value:** SF3B1 mutations in MDS are generally associated with a **favorable prognosis** and lower risk of transformation to AML. * **Treatment:** Luspatercept is a newer agent used specifically for anemia in MDS-RS patients. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 622-624.

Question 1

Analyze the provided pedigree chart to identify the underlying genetic disease.

Accepted Answer

Crouzon syndrome

Answer

Sickle cell anaemia

Answer

Diabetes insipidus

Answer

Hunter syndrome

Question 2

What is the most common tumor in females with tuberous sclerosis?

Accepted Answer

Angiomyolipoma

Answer

Rhabdomyosarcoma

Answer

Pulmonary lymphangioleiomyomatosis

Answer

Optic glioma

Question 3

What is a Leiden mutation?

Accepted Answer

Mis-sense mutation

Answer

Frame shift mutation

Answer

Tri nucleotide repeat mutation

Answer

Non-sense mutation

Question 4

All of the following are intermediate filaments except?

Accepted Answer

Cadherin

Answer

Lamin

Answer

Vimentin

Answer

Desmin

Question 5

What is the gene involved in GIST?

Accepted Answer

C-KIT

Answer

BRAC-1

Answer

p53

Answer

BRAC-2

Question 6

A patient died of Alzheimer's disease. At autopsy, the heart contains a yellow-brown, finely granular pigment. What is the most likely cause of this pigment?

Accepted Answer

Lipochrome, often referred to as 'wear and tear' pigment

Answer

Hemosiderin, indicating iron overload

Answer

Glycogen, suggestive of a glycogen storage disorder

Answer

Fat, associated with atherosclerosis

Question 7

Which of the following is a sign of chronic inflammation?

Accepted Answer

Angiogenesis

Answer

Purulent exudate

Answer

Induration

Answer

Edema

Question 8

What is the function of the FMR1 protein?

Accepted Answer

It is coded by the FMR1 gene which has the (5′-CGG-3′) n repeat segments.

Answer

It is expressed in fragile X-associated mental retardation.

Answer

It is normally found in the brain and ovaries.

Answer

When defective, it is not sufficient to cause the fragile X-associated mental retardation syndrome.

Question 9

Ring sideroblasts in myelodysplastic syndrome are associated with mutations in which gene?

Accepted Answer

SF3B1

Answer

ASXL1

Answer

EZH2

Answer

TET2

Question 10

Which stain is used for tissue fats?

Accepted Answer

Sudan IV

Answer

PAS

Answer

Prussian blue

Answer

Alcian blue

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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