Molecular Pathology Practice Questions

Q: Barr body is absent in which individuals?

Turner. ***Turner*** - Individuals with **Turner syndrome (45,X)** have only one X chromosome and therefore no Barr bodies, as Barr bodies form from extra X chromosomes [1]. - This condition results in various clinical features including **short stature** and **gonadal dysgenesis** [1]. *Kleinfelter* - **Klinefelter syndrome (47, XXY)** typically presents with one or more Barr bodies due to the presence of an additional X chromosome [1]. - Affected individuals usually exhibit **hypogonadism** and **gynecomastia** [1]. *None of the above* - This option suggests that all listed conditions have Barr bodies, which is incorrect since Turner syndrome does not. - Hence, it fails to identify the true condition characterized by the **absence of Barr bodies**. *Super female* - Super female refers to individuals with **47, XXX** karyotype, who have one Barr body due to the two extra X chromosomes. - They often present with normal female characteristics, thus having Barr bodies. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 173-177.

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.

Question 1

Barr body is absent in which individuals?

Accepted Answer

Turner

Answer

Super female

Answer

Klinefelter

Answer

None of the above

Question 2

Which of the following is a polygenic disorder?

Accepted Answer

Hypertension

Answer

Cystic fibrosis

Answer

Phenylketonuria

Answer

Multiple sclerosis

Question 3

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 4

Best sample for karyotyping is?

Accepted Answer

Blood

Answer

Bone marrow

Answer

Amniotic fluid

Answer

Chorionic villi

Question 5

Karyotyping is done in which phase of the cell cycle?

Accepted Answer

Metaphase

Answer

Anaphase

Answer

Telophase

Answer

S phase

Question 6

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 7

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 8

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

Accepted Answer

Overexpression

Answer

Suppression

Answer

Mutation

Answer

Translocation

Question 9

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 10

Which of the following is not a chromosome breakage disorder?

Accepted Answer

Duchenne muscular dystrophy

Answer

Bloom syndrome

Answer

Ataxia telangiectasia

Answer

Fanconi anemia

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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