Molecular Pathology Practice Questions

Q: Which of the following is a polygenic disorder?

Hypertension. ***Hypertension*** - **Hypertension** is a classic example of a **polygenic disorder**, meaning it is influenced by multiple genes acting together, often in combination with environmental factors. - The inheritance pattern is **complex and multifactorial**, making it difficult to predict based on a single genetic marker. *Cystic fibrosis* - **Cystic fibrosis** is a **monogenic disorder** caused by mutations in a single gene, the **CFTR gene** [1]. - It follows an **autosomal recessive** inheritance pattern, meaning two copies of the mutated gene are required for the disease to manifest [1]. *Phenylketonuria* - **Phenylketonuria (PKU)** is also a **monogenic disorder** caused by a mutation in the **PAH gene**, leading to a deficiency of the enzyme **phenylalanine hydroxylase**. - It is an **autosomal recessive** disorder, requiring two copies of the mutated gene. *Multiple sclerosis* - **Multiple sclerosis** is considered a **complex, multifactorial disorder** with both genetic and environmental components [1]. - While there is a genetic predisposition, it does not strictly fit the definition of a simple polygenic disorder where multiple genes directly cause the disease; instead, it involves interactions between many genes and the environment [1].

Q: Which of the following conditions is not inherited in an autosomal dominant manner?

Albinism. ***Albinism*** - Albinism is typically inherited in an **autosomal recessive** manner [2], not autosomal dominant. - It is caused by mutations in genes responsible for **melanin production**, leading to a lack of pigment in skin, hair, and eyes [2]. *Familial adenomatous polyposis* - This condition is an **autosomal dominant** disorder [1] characterized by the development of numerous polyps in the colon. - It is caused by mutations in the **APC** gene, significantly increasing the risk for colorectal cancer. *Von - Hippel Lindau syndrome* - Von Hippel Lindau syndrome is also an **autosomal dominant** disorder [1], associated with tumors in various organs, including hemangioblastomas and renal cell carcinoma. - This condition is caused by mutations in the **VHL** gene, leading to abnormal blood vessel growth. *Marfan's syndrome* - Marfan's syndrome is an **autosomal dominant** connective tissue disorder that affects various systems in the body, particularly the cardiovascular system. - It is caused by mutations in the **FBN1** gene, leading to tall stature, long limbs, and heart-related complications.

Q: Best sample for karyotyping is?

Blood. ***Blood*** - **Peripheral blood lymphocytes** are easily accessible and stimulate to divide in culture, providing sufficient metaphase cells for karyotyping. - This is the most common and least invasive method for routine **karyotyping** in adults and children. *Bone marrow* - While bone marrow cells can be used for karyotyping, especially in diagnosing **hematological malignancies**, it is a more invasive procedure than a blood draw [1]. - Bone marrow is primarily used when there is suspicion of a **chromosomal abnormality** specifically affecting hematopoietic cells, such as in leukemia [1]. *Amniotic fluid* - **Amniotic fluid** is collected via **amniocentesis** and contains fetal cells, making it suitable for prenatal karyotyping. - However, it is an **invasive procedure** reserved for specific prenatal diagnostic indications, not routine karyotyping in postnatal individuals. *Chorionic villi* - **Chorionic villi** are obtained via **chorionic villus sampling (CVS)** and provide fetal cells for early prenatal karyotyping. - Like amniotic fluid, CVS is an **invasive prenatal diagnostic** test and not the "best" or most common sample for general karyotyping. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 584-585.

Q: Karyotyping is done in which phase of the cell cycle?

Metaphase. ***Metaphase*** - During **metaphase**, chromosomes are maximally condensed and aligned at the **metaphase plate**, making them most visible and easy to distinguish under a microscope. - This condensation and alignment are crucial for accurate visualization and analysis of chromosome number and structure in **karyotyping**. *Anaphase* - In **anaphase**, sister chromatids separate and move to opposite poles, which makes them difficult to organize and analyze systematically for karyotyping. - The chromosomes are in motion and becoming less condensed as they move apart, which is not ideal for imaging. *Telophase* - During **telophase**, chromosomes decondense and nuclear envelopes reform, making them invisible or poorly defined for microscopic analysis. - The cell is also preparing to divide, and the chromosomes are no longer individually distinct structures suitable for karyotyping. *S phase* - The **S (synthesis) phase** is when DNA replication occurs, and chromosomes are replicated but remain in a decondensed state as chromatin. - In this phase, individual chromosomes are not condensed or visible as distinct structures, making them unsuitable for karyotyping.

Q: Which genetic mutation is most commonly associated with male breast carcinoma?

BRCA2 mutation. ***BRCA2 mutation*** - **BRCA2 mutations** are the most common genetic mutations found in men with **breast cancer**, significantly increasing their lifetime risk. - They are also associated with an increased risk of **prostate cancer**, **pancreatic cancer**, and **melanoma** in men. *TP53 mutation* - **TP53 mutations** are associated with **Li-Fraumeni syndrome**, a hereditary cancer syndrome that increases the risk of various cancers, including sarcomas, brain tumors, and early-onset breast cancer in women. - While it can increase breast cancer risk, it is less commonly associated with **male breast carcinoma** compared to BRCA2. *PALB2 mutation* - **PALB2 (Partner And Localizer of BRCA2) mutations** are associated with an increased risk of breast cancer in both men and women, acting in concert with BRCA2. - While impactful, they are less prevalent than **BRCA2 mutations** in male breast cancer overall. *BRCA1 mutation* - **BRCA1 mutations** primarily increase the risk of breast and ovarian cancer in women. While they can increase the risk of **male breast cancer** to some extent, their contribution is much lower than that of **BRCA2 mutations** [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1058-1059.

Q: The given karyotype is seen in which of the following syndromes?

Down syndrome. ***Correct: Down syndrome*** - The karyotype shows **trisomy 21** (47 chromosomes with an extra chromosome 21), which causes **Down syndrome**. - This is the most common chromosomal abnormality, with characteristic karyotype showing **three copies of chromosome 21**. - Clinical features include intellectual disability, characteristic facies, and congenital heart defects. *Incorrect: Angelman syndrome* - Caused by **deletion or mutation of UBE3A gene** on chromosome 15, not trisomy 21. - Shows normal chromosomal number (46 chromosomes), unlike the **47 chromosomes** seen in this karyotype. - Characterized by developmental delay, seizures, and happy demeanor. *Incorrect: Fragile X syndrome* - Results from **CGG repeat expansion** in the FMR1 gene on the X chromosome. - Typically shows **normal karyotype structure** (46 chromosomes), not the **extra chromosome 21** visible here. - Most common inherited cause of intellectual disability. *Incorrect: Cri du chat syndrome* - Caused by **deletion on chromosome 5p**, which would show as a **missing chromosomal segment**. - The karyotype would show **46 chromosomes with 5p deletion**, not **47 chromosomes with trisomy 21**. - Named for characteristic cat-like cry in infancy. *Incorrect: Turner syndrome* - Results from **missing X chromosome** (45,X karyotype) in females. - Shows **45 chromosomes total**, not the **47 chromosomes with extra chromosome 21** seen here. - Presents with short stature and ovarian dysgenesis.

Q: In breast cancer, Her-2/Neu promotes tumorigenesis by what mechanism?

Overexpression. ***Promoting cell proliferation through overexpression*** - Overexpression of Her-2/Neu leads to increased **cell proliferation**, a key feature in the progression of breast cancer [1,2]. - It is often associated with **aggressive tumor behavior** and poorer prognosis in patients [1]. *Alteration in gene expression* - While Her-2/Neu may influence gene expression, it primarily functions through **signaling pathways** that promote cell division rather than through alteration itself. - This oes not directly correlate with the specific impact of Her-2/Neu in tumor progression. *Gene amplification* - Gene amplification refers to the increased number of copies of the Her-2 gene, but does not directly describe its role in empowered **proliferation** or tumor advancement [1,3]. - This process is a mechanism but doesn't explain how it promotes cancer progression effectively. *Inhibiting tumor growth* - Her-2/Neu does not inhibit tumor growth; rather, it is **associated with aggressive growth** and poor prognosis in breast cancer [1]. - This ontradicts the established role of Her-2/Neu in promoting cancer rather than suppressing it. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, p. 1066. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1059-1060. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 292.

Q: Which of the following disorders is most commonly associated with multifactorial inheritance?

Cleft lip. ***Cleft lip*** - **Cleft lip** is a classic example of a **multifactorial disorder**, resulting from the interaction of multiple genes and environmental factors. - Its recurrence risk is typically observed to be around 2-5% in affected families, consistent with **multifactorial inheritance**. *Achondroplasia* - Achondroplasia is an **autosomal dominant disorder**, caused by a single gene mutation in the **FGFR3 gene**. - It does not primarily involve the complex interplay of multiple genes and environmental factors characteristic of multifactorial inheritance. *Lysosomal storage disease* - Lysosomal storage diseases are a group of **autosomal recessive disorders**, each caused by a defect in a specific lysosomal enzyme. - They follow classic **Mendelian inheritance patterns** rather than multifactorial models. *Huntington disease* - Huntington disease is an **autosomal dominant neurodegenerative disorder**, caused by a trinucleotide repeat expansion in the **HTT gene**. - It exhibits a clear dominant inheritance pattern and does not involve multiple genes or significant environmental contributions in its etiology.

Q: Which of the following is not a chromosome breakage disorder?

Duchenne muscular dystrophy. ***Duchenne muscular dystrophy*** - Duchenne muscular dystrophy is primarily a **muscle degeneration disorder** caused by mutations in the **dystrophin gene**, not a chromosome breakage disorder. - It does not involve issues with **chromosomal stability** or breakage, unlike the others listed. *Ataxia telangiectasia* - Ataxia telangiectasia is associated with defects in **DNA repair mechanisms**, leading to **chromosome breakage** and instability [1]. - Patients exhibit progressive **ataxia**, **telangiectasia**, and increased sensitivity to radiation. *Fanconi anemia* - Fanconi anemia is characterized by a defect in the **DNA repair pathway**, resulting in increased **chromosome breakage** [1]. - It is associated with **bone marrow failure** and development of various malignancies. *Bloom syndrome* - Bloom syndrome results from defects in the **BLM gene**, leading to **genomic instability** and an increased rate of chromosome breakage [1]. - This condition causes symptoms like **short stature**, **facial lesions**, and a predisposition to cancer. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 322-323.

Q: Which banding technique is most commonly used for karyotyping?

G banding. ***G banding*** - This method is the **most widely used** technique for karyotyping, allowing clear visualization of chromosome bands under light microscopy [1][2]. - G banding helps in identifying **chromosomal abnormalities** and is routinely utilized in clinical genetics [2]. *C banding* - Primarily highlights the **centromeric regions** of chromosomes, but is less common than G banding for overall karyotyping. - Does not provide a full **karyotype view**, making it less suitable for routine analysis. *R banding* - Useful for providing **reverse staining**, which shows the bands in a different manner but is not as commonly employed in clinical settings. - Typically used to analyze specific **chromosomal translocations**, rather than routine karyotyping. *Q banding* - This technique involves **fluorescent microscopy** to visualize chromosomes but is not as prevalent for basic karyotyping. - Mainly used for detecting **specific chromosomal anomalies**, not the standard karyotype assessment. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 54-55. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 167-168.

Question 1

Which of the following is a polygenic disorder?

Accepted Answer

Hypertension

Answer

Cystic fibrosis

Answer

Phenylketonuria

Answer

Multiple sclerosis

Question 2

Which of the following conditions is not inherited in an autosomal dominant manner?

Accepted Answer

Albinism

Answer

Von - Hippel Lindau syndrome

Answer

Marfan's syndrome

Answer

Familial adenomatous polyposis

Question 3

Best sample for karyotyping is?

Accepted Answer

Blood

Answer

Bone marrow

Answer

Amniotic fluid

Answer

Chorionic villi

Question 4

Karyotyping is done in which phase of the cell cycle?

Accepted Answer

Metaphase

Answer

Anaphase

Answer

Telophase

Answer

S phase

Question 5

Which genetic mutation is most commonly associated with male breast carcinoma?

Accepted Answer

BRCA2 mutation

Answer

TP53 mutation

Answer

PALB2 mutation

Answer

BRCA1 mutation

Question 6

The given karyotype is seen in which of the following syndromes?

Accepted Answer

Down syndrome

Answer

Angelman syndrome

Answer

Fragile x syndrome

Answer

Turner syndrome

Question 7

In breast cancer, Her-2/Neu promotes tumorigenesis by what mechanism?

Accepted Answer

Overexpression

Answer

Suppression

Answer

Mutation

Answer

Translocation

Question 8

Which of the following disorders is most commonly associated with multifactorial inheritance?

Accepted Answer

Cleft lip

Answer

Achondroplasia

Answer

Lysosomal storage disease

Answer

Huntington disease

Question 9

Which of the following is not a chromosome breakage disorder?

Accepted Answer

Duchenne muscular dystrophy

Answer

Bloom syndrome

Answer

Ataxia telangiectasia

Answer

Fanconi anemia

Question 10

Which banding technique is most commonly used for karyotyping?

Accepted Answer

G banding

Answer

Q banding

Answer

C banding

Answer

R banding

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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