Molecular Pathology Practice Questions

Q: In Down syndrome, the chromosomal abnormality is most commonly due to which of the following?

Maternal nondisjunction. **Explanation:** **1. Why Maternal Nondisjunction is Correct:** Down syndrome (Trisomy 21) is primarily caused by **meiotic nondisjunction**, where chromosomes fail to separate during gametogenesis. In approximately **95% of cases**, the extra chromosome 21 is derived from the mother. This occurs most frequently during **Meiosis I**. The risk of maternal nondisjunction increases significantly with **advanced maternal age** (typically >35 years) due to the prolonged "dictyotene" stage (prophase I) in which oocytes are arrested from fetal life until ovulation. **2. Analysis of Incorrect Options:** * **Translocation (Option A):** Accounts for only **3–4%** of cases (Robertsonian translocation, usually between chromosomes 14 and 21). Unlike nondisjunction, this is independent of maternal age and can be inherited from a carrier parent. * **Point Mutations (Option B):** Down syndrome is a **numerical chromosomal aberration** (aneuploidy), not a single-gene disorder or a change in the DNA sequence at a specific locus. * **Paternal Nondisjunction (Option C):** While nondisjunction can occur during spermatogenesis, it accounts for only about **5%** of Down syndrome cases. **3. High-Yield Clinical Pearls for NEET-PG:** * **Most common cause:** Maternal Meiosis I nondisjunction (95%). * **Mosaicism:** Accounts for ~1–2% of cases; caused by **mitotic** nondisjunction during early embryogenesis. * **Biochemical Screening (Quadruple Test):** Characterized by **decreased** AFP and Estriol, and **increased** hCG and Inhibin-A (Mnemonic: **HI** is **High** – **H**CG and **I**nhibin). * **First Trimester Screening:** Increased Nuchal Translucency (NT) and decreased PAPP-A. * **Associated Pathology:** Early-onset Alzheimer’s (APP gene on Ch 21), Endocardial cushion defects (ASD/VSD), and increased risk of ALL/AML (M7).

Q: A pedigree chart shows the following pattern of inheritance. What is the most likely mode of inheritance?

Autosomal recessive. ***Autosomal recessive*** - Characterized by **unaffected carrier parents** producing affected offspring, with the trait **skipping generations**. - Affects **both sexes equally** and typically shows a **horizontal pattern** within a single generation. *Autosomal dominant* - Shows a **vertical pattern** where affected individuals have at least one affected parent in each generation. - Does **not skip generations** and demonstrates continuous transmission from parent to child. *X-linked recessive* - Primarily affects **males** with a characteristic pattern of affected grandfathers passing the trait through **carrier daughters** to affected grandsons. - Shows **no male-to-male transmission** since fathers cannot pass X-linked traits to their sons. *X-linked dominant* - Affects **more females than males** and shows transmission from affected fathers to **all daughters** but no sons. - Demonstrates a **vertical pattern** with affected individuals in consecutive generations, unlike the skipping seen in autosomal recessive.

Q: The HER2/neu receptor plays a role in what?

Predicting therapeutic response. **Explanation:** The **HER2/neu (Human Epidermal Growth Factor Receptor 2)** is a proto-oncogene located on chromosome 17 [3]. Its overexpression occurs in approximately 15–20% of breast cancers and serves as a critical **predictive marker** [1]. **Why Option A is correct:** HER2 status is primarily used to **predict therapeutic response** to targeted therapies. Patients who are HER2-positive respond specifically to monoclonal antibodies like **Trastuzumab (Herceptin)** and Pertuzumab [1]. These drugs block the extracellular domain of the receptor, inhibiting downstream signaling that promotes cell proliferation. **Analysis of Incorrect Options:** * **Option B (Diagnosis):** Breast cancer is diagnosed via clinical examination, imaging (Mammography/USG), and confirmed by histopathology (Biopsy). HER2 is a molecular marker used *after* diagnosis to characterize the tumor. * **Option C (Screening):** Screening is done via Mammography in the general population. Molecular markers are never used for screening. * **Option D (Recurrence):** While HER2 positivity is associated with a more aggressive clinical course and higher risk of recurrence (prognostic value), its primary clinical utility in modern oncology is guiding the choice of therapy [2]. **High-Yield Clinical Pearls for NEET-PG:** * **Prognostic vs. Predictive:** HER2 is both. It is **prognostic** (indicates poor prognosis/aggressive tumor) and **predictive** (indicates likely response to Trastuzumab) [1]. * **Testing Method:** Initial screening is done via **Immunohistochemistry (IHC)**. If IHC results are equivocal (2+), **FISH (Fluorescence In Situ Hybridization)** is the gold standard to confirm gene amplification [2]. * **Side Effect:** Trastuzumab is associated with **cardiotoxicity** (reversible decrease in LVEF), unlike anthracyclines which cause irreversible damage.

Q: Which of the following chromosomes is involved in Patau syndrome?

Chromosome 13. **Explanation:** **Patau syndrome** is a severe genetic disorder caused by **Trisomy 13** (the presence of an extra copy of chromosome 13). It is the least common and most severe of the three viable autosomal trisomies. The condition results from meiotic non-disjunction, most commonly associated with advanced maternal age. **Analysis of Options:** * **Option A (Chromosome 13): Correct.** Patau syndrome is characterized by a "triad" of clinical features: **Microphthalmia** (small eyes), **Cleft lip/palate**, and **Polydactyly** (extra fingers/toes). Other features include holoprosencephaly and cutis aplasia (scalp defects). * **Option B (Chromosome 18): Incorrect.** Trisomy 18 is **Edwards syndrome**. Clinical hallmarks include "rocker-bottom feet," clenched fists with overlapping fingers, and micrognathia (small jaw). * **Option C (Chromosome 21): Incorrect.** Trisomy 21 is **Down syndrome**, the most common viable trisomy. It is characterized by intellectual disability, flat facial profile, Simian crease, and an increased risk of early-onset Alzheimer’s and ALL/AML. * **Option D (Chromosome 5): Incorrect.** A terminal deletion of the short arm of chromosome 5 (5p-) leads to **Cri-du-chat syndrome**, characterized by a high-pitched, cat-like cry and microcephaly. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Trisomies:** **P**atau (13 - **P**uberty starts at 13), **E**dwards (18 - **E**lection age is 18), **D**own (21 - **D**rinking age is 21). * **Biochemical Screening:** In Patau syndrome, first-semester screening typically shows **decreased free β-hCG and PAPP-A**. * **Prognosis:** Most infants with Patau syndrome die within the first few days or months of life due to severe neurological or cardiac complications.

Question 1

In Down syndrome, the chromosomal abnormality is most commonly due to which of the following?

Accepted Answer

Maternal nondisjunction

Answer

Translocation

Answer

Point mutations

Answer

Paternal nondisjunction

Question 2

Most common cause of Down's syndrome is:

Accepted Answer

Trisomy 21

Answer

Monosomy 21

Answer

Robertsonian translocation

Answer

Mosaicism

Question 3

45X0 is the chromosomal abnormality seen in which of the following conditions?

Accepted Answer

Turner's syndrome

Answer

Down's syndrome

Answer

Klinefelter's syndrome

Answer

True hermaphroditism

Question 4

Which of the following is an example of a gain-of-function mutation?

Accepted Answer

Huntington's disease

Answer

Osteogenesis imperfecta

Answer

Ehlers-Danlos syndrome

Answer

Marfan syndrome

Question 5

A pedigree chart shows the following pattern of inheritance. What is the most likely mode of inheritance?

Accepted Answer

Autosomal recessive

Answer

Autosomal dominant

Answer

X-linked recessive

Answer

X-linked dominant

Question 6

The HER2/neu receptor plays a role in what?

Accepted Answer

Predicting therapeutic response

Answer

Diagnosis of breast cancer

Answer

Screening of breast cancer

Answer

Recurrence of tumor

Question 7

Germline mutations in which of the following genes are not associated with hereditary breast cancer?

Accepted Answer

GATA2

Answer

CHEK2

Answer

BRCA2

Answer

TP53

Question 8

Which of the following chromosomes is involved in Patau syndrome?

Accepted Answer

Chromosome 13

Answer

Chromosome 18

Answer

Chromosome 21

Answer

Chromosome 5

Question 9

What is the most common tumor diagnosed in a female patient with tuberous sclerosis?

Accepted Answer

Renal Angiomyolipoma

Answer

Rhabdomyosarcoma

Answer

Pulmonary lymphangioleiomyomatosis

Answer

Optic glioma

Question 10

Beal's syndrome is caused due to a defect in which of the following genes?

Accepted Answer

Fibrillin-2

Answer

Fibrillin-1 gene

Answer

Elastin

Answer

Lamillin

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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