Molecular Pathology Practice Questions

Q: What is the term for a single gene defect that causes multiple, seemingly unrelated problems?

Pleiotropism. **Explanation:** **1. Why Pleiotropism is Correct:** **Pleiotropism** occurs when a single gene mutation results in multiple, diverse phenotypic effects across different organ systems [1]. These effects often seem unrelated but share a common underlying biochemical or structural defect. * **Classic Example:** **Marfan Syndrome**. A mutation in the *FBN1* gene (encoding Fibrillin-1) leads to defects in the skeletal system (arachnodactyly), the ocular system (ectopia lentis), and the cardiovascular system (aortic aneurysm). **2. Why Other Options are Incorrect:** * **Pseudodominance:** This occurs when a recessive trait mimics a dominant pattern of inheritance. This happens when a person homozygous for a recessive trait mates with a heterozygote carrier, resulting in a 50% chance of affected offspring in every generation. * **Penetrance:** This refers to the percentage of individuals with a specific genotype who actually express the associated phenotype. If 100 people have the gene but only 80 show symptoms, it is "incomplete penetrance." * **Anticipation:** This is the phenomenon where a genetic disorder becomes more severe or has an earlier age of onset in successive generations. It is typically seen in **Trinucleotide Repeat Disorders** (e.g., Huntington’s disease, Fragile X syndrome). **3. Clinical Pearls for NEET-PG:** * **Variable Expressivity:** Unlike penetrance (all-or-none), this refers to the *degree* or severity of the phenotype among individuals with the same genotype. * **Locus Heterogeneity:** Mutations at different loci (different genes) produce the same phenotype (e.g., Albinism, Osteogenesis Imperfecta). * **Allelic Heterogeneity:** Different mutations within the *same* gene produce the same phenotype (e.g., Cystic Fibrosis, Beta-thalassemia). * **High-Yield Pleiotropy Example:** **Phenylketonuria (PKU)** causes mental retardation, reduced hair pigmentation, and a "mousy" odor.

Q: Study the following pedigree. What is the inheritance pattern of the disease in the family?

X-linked recessive type. ***X-linked recessive type*** - **Affected males** appear across multiple generations connected through **unaffected carrier females**, which is characteristic of X-linked recessive inheritance. - There is **no male-to-male transmission** since fathers cannot pass their X chromosome to sons, and **daughters of affected males** are obligate carriers. *Autosomal recessive type* - Would require **both parents to be carriers** for affected offspring, typically showing affected individuals in a single generation (horizontal pattern). - **Consanguinity** is often present, and both **males and females** are equally affected, which doesn't match the pedigree pattern. *Autosomal dominant type* - Would show **vertical transmission** with affected individuals in every generation having at least one affected parent. - **Male-to-male transmission** would be possible, and approximately **50% of offspring** from affected parents would be affected. *X-Linked dominant type* - **All daughters** of affected males would be affected since they must inherit the father's X chromosome. - Affected females would have **more severely affected offspring** than the pattern typically shows, and there would be more affected females overall.

Q: Which of the following chromosomal abnormalities is NOT typically associated with Down Syndrome?

Translocation (11;14). ### Explanation Down Syndrome (Trisomy 21) is the most common chromosomal disorder causing intellectual disability. It results from an extra copy of genetic material on **Chromosome 21**. **Why Option C is Correct:** **Translocation (11;14)** involves chromosomes 11 and 14. This specific translocation is classically associated with **Mantle Cell Lymphoma**, not Down Syndrome. Since it does not involve chromosome 21, it cannot result in the phenotypic expression of Down Syndrome. **Analysis of Incorrect Options:** * **Option B (Trisomy 21):** This is the most common cause (95% of cases), usually due to **maternal meiotic non-disjunction**. * **Options A & D (Robertsonian Translocations):** Approximately 3–4% of Down Syndrome cases are due to translocations. In these cases, the long arm of chromosome 21 attaches to another acrocentric chromosome. The most common partner is **chromosome 14** [t(14;21)], followed by **chromosome 15** [t(15;21)] and chromosome 22. Unlike non-disjunction, translocation-related Down Syndrome can be inherited from a carrier parent, leading to a high recurrence risk in future pregnancies. **High-Yield Clinical Pearls for NEET-PG:** * **Most common cause:** Meiotic non-disjunction (correlated with advanced maternal age). * **Recurrence Risk:** If a parent is a carrier of a **21;21 translocation**, the risk of Down Syndrome in the offspring is **100%**. * **Screening:** Low AFP, low unconjugated estriol (uE3), and high hCG/Inhibin-A are seen in the second-trimester quadruple screen. * **Cardiac:** Endocardial cushion defects (ASD/VSD) are the most common congenital heart diseases. * **GI:** Duodenal atresia ("Double bubble" sign) and Hirschsprung disease.

Q: The RET proto-oncogene is located on which chromosome?

Chromosome 10. **Explanation:** The **RET (REarranged during Transfection)** proto-oncogene is located on the long arm of **Chromosome 10 (10q11.2)**. It encodes a receptor tyrosine kinase essential for the development of the neural crest-derived cells and the genitourinary system. **Why Chromosome 10 is correct:** The RET gene is a classic example of a proto-oncogene that can be activated by two distinct mechanisms: 1. **Point Mutations:** Germline mutations lead to **Multiple Endocrine Neoplasia (MEN) syndromes 2A and 2B**, as well as Familial Medullary Thyroid Carcinoma (FMTC) [1]. 2. **Gene Rearrangements:** Chromosomal translocations involving RET lead to **Papillary Thyroid Carcinoma (PTC)**, specifically the RET/PTC rearrangements [1]. **Analysis of Incorrect Options:** * **Chromosome 9:** Associated with the **ABL** proto-oncogene (involved in the t(9;22) Philadelphia chromosome in CML). * **Chromosome 11:** Home to the **WT1** (Wilms tumor) gene and the **CCND1** (Cyclin D1) gene, often involved in Mantle Cell Lymphoma via t(11;14). * **Chromosome 12:** Associated with the **KRAS** oncogene and the **MDM2** gene (often amplified in liposarcomas). **High-Yield Clinical Pearls for NEET-PG:** * **Gain-of-function** mutations in RET → MEN 2A, MEN 2B, and Medullary Thyroid Carcinoma [1]. * **Loss-of-function** mutations in RET → **Hirschsprung disease** (congenital megacolon). * **MEN 2A:** Medullary Thyroid Ca, Pheochromocytoma, Parathyroid Hyperplasia [1]. * **MEN 2B:** Medullary Thyroid Ca, Pheochromocytoma, Mucosal Neuromas, and Marfanoid habitus [1]. * Prophylactic thyroidectomy is often indicated in children carrying RET mutations to prevent aggressive Medullary Thyroid Carcinoma. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1097-1137.

Question 1

What is the term for a single gene defect that causes multiple, seemingly unrelated problems?

Accepted Answer

Pleiotropism

Answer

Pseudodominance

Answer

Penetrance

Answer

Anticipation

Question 2

Which method is used to detect the BCR-ABL fusion gene?

Accepted Answer

FISH

Answer

Flow cytometry

Answer

Karyotyping

Answer

RT-PCR

Question 3

Which of the following is NOT an advantage of nanotechnology in cancer diagnosis?

Accepted Answer

Nanocrystals exhibit a narrow difference between their excitation and emission peak spectra.

Answer

Nanocrystals exhibit bright, photostable fluorescence.

Answer

Nanocrystals have a narrow spectrum wavelength.

Answer

Peak spectrum wavelength is tunable.

Question 4

A 38-year-old woman shows evidence of early cataracts, hair loss, atrophy of skin, osteoporosis, and accelerated atherosclerosis. This patient has most likely inherited mutations in both alleles of a gene that encodes which of the following types of intracellular proteins?

Accepted Answer

Helicase

Answer

Deaminase

Answer

Oxidase

Answer

Polymerase

Question 5

Study the following pedigree. What is the inheritance pattern of the disease in the family?

Accepted Answer

X-linked recessive type

Answer

Autosomal recessive type

Answer

Autosomal dominant type

Answer

X-Linked dominant type

Question 6

Turner syndrome is characterized by which chromosomal abnormality?

Accepted Answer

45, XO

Answer

47, XXY

Answer

Trisomy 13

Answer

Trisomy 18

Question 7

Translocation between two acrocentric chromosomes occurs with breakpoints near the centromeres, resulting in very large and very small chromosomes. The smaller fragment is typically lost. What is this type of cytogenetic abnormality?

Accepted Answer

Robertsonian translocation

Answer

Deletion

Answer

Balanced translocation

Answer

Inversion

Question 8

Which of the following chromosomal abnormalities is NOT typically associated with Down Syndrome?

Accepted Answer

Translocation (11;14)

Answer

Translocation (14;21)

Answer

Trisomy 21

Answer

Translocation (15;21)

Question 9

The RET proto-oncogene is located on which chromosome?

Accepted Answer

Chromosome 10

Answer

Chromosome 9

Answer

Chromosome 11

Answer

Chromosome 12

Question 10

What is the most common trisomy?

Accepted Answer

Trisomy 16

Answer

Trisomy 21

Answer

Trisomy 18

Answer

Trisomy 13

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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