Molecular Pathology Practice Questions

Q: A karyotyping image is given below. What are the clinical features most likely to be expected in such patients?

Gynecomastia and long limbs. ***Gynecomastia and long limbs*** - The karyotype shows **47, XXY**, which is characteristic of **Klinefelter syndrome** [1]. - **Gynecomastia** (breast development in males) and disproportionately **long limbs** with tall stature [1] are classic features of Klinefelter syndrome due to the extra X chromosome. - Other features include small testes, infertility, and reduced secondary sexual characteristics [1]. *Flat occiput* - **Flat occiput** is a characteristic feature of **Down syndrome** (Trisomy 21), which shows karyotype 47, XX or XY, +21. - The given karyotype shows a normal set of autosomes with normal chromosome 21 count, ruling out Down syndrome. *Epicanthal folds and single palmar crease* - These are also characteristic features of **Down syndrome** (Trisomy 21). - **Epicanthal folds** (skin folds at the inner corner of the eyes) and **single palmar crease** (simian crease) are common dysmorphic features in trisomy 21. - The karyotype shown is 47, XXY, not trisomy 21. *Webbed neck and shield chest* - **Webbed neck** and **shield chest** are characteristic features of **Turner syndrome** (45, X) [1]. - Turner syndrome affects phenotypic females with monosomy X, showing karyotype 45, X [1]. - The given karyotype shows 47, XXY with male sex chromosomes (XY + extra X), not monosomy X. **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 true? 1. BRCA1 is an oncogene 2. HER2neu is amplified only in a fraction of breast cancer 3. EGFR (+) is seen in non-small cell lung cancer 4. N-MYC is a tumor suppressor gene

2,3. ***Correct Option: 2,3*** - **Statement 2 is TRUE**: HER2neu amplification occurs in only a fraction (~15-20%) of breast cancers, making it a specific subset requiring targeted therapy with trastuzumab (Herceptin) [1]. - **Statement 3 is TRUE**: EGFR (epidermal growth factor receptor) mutations or overexpression are commonly seen in non-small cell lung cancer (NSCLC) and serve as important therapeutic targets for tyrosine kinase inhibitors. *Incorrect Option: 1,3* - Statement 1 is **FALSE**: BRCA1 is a **tumor suppressor gene**, not an oncogene. It functions in DNA double-strand break repair, and loss-of-function mutations increase the risk of breast and ovarian cancers. - Statement 3 is TRUE, but the inclusion of the false statement about BRCA1 makes this option incorrect. *Incorrect Option: 1,2* - Statement 1 is **FALSE**: BRCA1 is a **tumor suppressor gene**, not an oncogene. - Statement 2 is TRUE [1], but the false classification of BRCA1 invalidates this option. *Incorrect Option: All of the options* - Statement 1 is **FALSE**: BRCA1 is a tumor suppressor gene, not an oncogene. - Statement 4 is **FALSE**: N-MYC is an **oncogene** that is amplified in neuroblastoma and other cancers, not a tumor suppressor gene. - Since two of the four statements are incorrect, "All of the options" cannot be true. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1059-1060.

Q: Which of the following is an Autosomal Dominant disease?

Von Willebrand disease. ***Von Willebrand disease*** - This is an **autosomal dominant** inherited disorder caused by a deficiency or dysfunction of **von Willebrand factor**, crucial for normal hemostasis [1], [2]. - It often presents with **mucocutaneous bleeding** like nosebleeds, easy bruising, and heavy menstrual bleeding [2]. *Wilson's disease* - This is an **autosomal recessive** disorder characterized by defective copper metabolism and accumulation in various organs, most notably the liver and brain. - Clinical features include **hepatic dysfunction**, neurologic symptoms like **tremors**, and **Kayser-Fleischer rings** in the eyes. *Cystic fibrosis* - This is an **autosomal recessive** disorder caused by mutations in the **CFTR gene**, leading to abnormal chloride transport. - It primarily affects the lungs and digestive system, causing **thick mucus production** and recurrent infections. *Friedreich's ataxia* - This is an **autosomal recessive** neurodegenerative disorder typically caused by a **GAA trinucleotide repeat expansion** in the FXN gene. - Key symptoms include progressive **ataxia**, dysarthria, and often heart problems.

Q: Barr body is NOT seen in:

Turner syndrome. ***Turner syndrome*** - Females with **Turner syndrome** have a **45, X0 karyotype**, meaning they only have one X chromosome [1]. - The **Barr body** is formed by the inactivation of one of the two X chromosomes in females, so its absence indicates only one X chromosome [1]. *Marfan's syndrome* - **Marfan's syndrome** is an autosomal dominant disorder affecting connective tissue, caused by a mutation in the **FBN1 gene** on chromosome 15. - The presence or absence of a Barr body is not directly related to Marfan's syndrome as it affects both males and females, and females would still have a Barr body. *Down's syndrome* - **Down's syndrome** is caused by **trisomy 21**, an extra copy of chromosome 21. - The presence or absence of a Barr body is determined by the number of X chromosomes, and individuals with Down's syndrome, if female, would still have a Barr body. *Klinefelter syndrome* - Individuals with **Klinefelter syndrome** have a **47, XXY karyotype**, possessing at least two X chromosomes and one Y chromosome. - This condition is characterized by the presence of a **Barr body** due to the inactivation of one of the multiple X chromosomes. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 175-177.

Q: Which of the following childhood tumor uses N-myc gene amplification for its prognosis?

Neuroblastoma. ***Neuroblastoma*** - **N-myc gene amplification** is a crucial **prognostic indicator** in neuroblastoma, correlating with aggressive disease and poor outcomes [1]. - Neuroblastoma is a **childhood cancer of neural crest origin**, often presenting as an adrenal mass or in sympathetic ganglia. *Nephroblastoma* - Also known as **Wilms tumor**, it is a childhood kidney cancer. - Its prognosis is more strongly associated with histology (e.g., **anaplasia**) and specific gene mutations like **WT1**, not N-myc amplification. *Retinoblastoma* - This is a **childhood eye cancer**. - Its prognosis is primarily linked to the presence of **RB1 gene mutations** and the extent of retinoblastoma gene protein (pRB) expression, not N-myc. *Rhabdomyosarcoma* - An aggressive **childhood soft tissue sarcoma** with skeletal muscle differentiation. - Prognostic factors often include clinical staging, histology (e.g., **alveolar vs. embryonal**), and specific genetic translocations like **PAX-FOXO1**, rather than N-myc amplification. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 486-487.

Q: A 25-year-old woman with amenorrhea has never had menarche. On physical examination, she is 145 cm (4 ft 9 in) tall. She has a webbed neck, a broad chest, and widely spaced nipples. Strong pulses are palpable in the upper extremities, but there are only weak pulses in the lower extremities. On abdominal MR imaging, her ovaries are small, elongated, and tubular. Which of the following karyotypes is she most likely to have?

45, X/46, XX. ***45, X/46, XX*** - The mosaic karyotype **45, X/46, XX** is a common variant of **Turner syndrome** [1]. This explains the patient's features like **short stature** [3], **webbed neck**, **broad chest**, **widely spaced nipples**, **streak gonads** (small, elongated, tubular ovaries leading to primary amenorrhea) [2], and **coarctation of the aorta** (strong upper extremity pulses, weak lower extremity pulses) [2]. - **Turner syndrome** is characterized by the absence of all or part of one of the X chromosomes, either outright (45, X) [3] or in a mosaic pattern (45, X/46, XX), leading to ovarian dysgenesis and somatic abnormalities [2]. *47, XXX* - A **47, XXX** karyotype, also known as **Triple X syndrome**, typically presents with phenotypically normal females, although tall stature, learning disabilities, and speech delays can occur [1]. - It does not cause the characteristic physical stigmata of Turner syndrome such as short stature, webbed neck, or cardiovascular defects, nor does it typically lead to streak gonads with primary amenorrhea. *47, XXY* - A **47, XXY** karyotype is characteristic of **Klinefelter syndrome**, which affects males [1], [3]. - Individuals with Klinefelter syndrome present with features such as tall stature, small testes, gynecomastia, and infertility, which are inconsistent with the patient's female gender and reported symptoms. *46, X, X (fra)* - A **46, X, X (fra)** karyotype refers to a normal female karyotype with a **fragile site** on an X chromosome. This is not a recognized cause of the constellation of symptoms described, which are classic for Turner syndrome. - While fragile sites can be associated with certain genetic conditions, they do not explain the specific physical and cardiovascular abnormalities or ovarian dysgenesis seen in this patient.

Q: BRCA1 gene lies on chromosome

17. ***Correct: 17*** - The **BRCA1 gene** is located on the long arm (q arm) of **chromosome 17** at position 21 (17q21). - This gene is a **tumor suppressor gene** involved in DNA repair, and mutations are strongly associated with increased risk of breast and ovarian cancers. *Incorrect: 18* - Chromosome 18 is associated with different genetic conditions, such as **Edwards syndrome** (trisomy 18), but not directly with BRCA1. - No major tumor suppressor genes like BRCA1 are primarily located on chromosome 18. *Incorrect: 21* - Chromosome 21 is known for being related to **Down syndrome** (trisomy 21). - It does not house the BRCA1 gene. *Incorrect: 20* - While chromosome 20 contains genes involved in various functions, it is **not the location of the BRCA1 gene**. - No significant link between BRCA1 and chromosome 20 has been identified.

Q: Number of chromosomes in Klinefelter syndrome:

47. ***47*** - **Klinefelter syndrome** is a genetic condition in males characterized by the presence of an extra X chromosome, resulting in a **47, XXY karyotype** [1]. - This additional chromosome increases the total count from the typical 46 to **47** [1]. *44* - A count of 44 chromosomes would indicate either a severe **aneuploidy** or a **haploid** state, which is not compatible with human life in a full somatic cell. - Normal human somatic cells contain 46 chromosomes (2n). *46* - A count of 46 chromosomes represents the **normal diploid number** for human somatic cells (46, XX for females and 46, XY for males). - This count would signify a genetically typical individual, not someone with Klinefelter syndrome. *45* - A count of 45 chromosomes typically indicates a **monosomy**, such as **Turner syndrome** (45, X) in females, where one sex chromosome is missing. - This is a different chromosomal abnormality from Klinefelter syndrome, which involves an extra chromosome. **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. 92-93.

Question 1

Match the following?
a. Trisomy 13 1. Huntington disease
b. Trisomy 18 2. Patau syndrome
c. Trinucleotide repeat sequence 3. Sickle cell disease
d. Hb point mutation of glutamate to valine 4. Edward syndrome

Accepted Answer

a2-b4-c1-d3

Answer

b1-a3-d2-c4

Answer

a2-b1-c4-d3

Answer

a4-b1-c3-d2

Question 2

Fluorescence in situ hybridization (FISH) is required in which of the following interpretations of Her2/neu?

Accepted Answer

2+

Answer

All of the options

Answer

1+

Answer

3+

Question 3

A karyotyping image is given below. What are the clinical features most likely to be expected in such patients?

Accepted Answer

Gynecomastia and long limbs

Answer

Flat occiput

Answer

Webbed neck and shield chest

Answer

Epicanthal folds and single palmar crease

Question 4

Which of the following is true?

1. BRCA1 is an oncogene
2. HER2neu is amplified only in a fraction of breast cancer
3. EGFR (+) is seen in non-small cell lung cancer
4. N-MYC is a tumor suppressor gene

Accepted Answer

2,3

Answer

1,3

Answer

1,2

Answer

All of the options

Question 5

Which of the following is an Autosomal Dominant disease?

Accepted Answer

Von Willebrand disease

Answer

Wilson's disease

Answer

Cystic fibrosis

Answer

Friedreich's ataxia

Question 6

Barr body is NOT seen in:

Accepted Answer

Turner syndrome

Answer

Marfan's syndrome

Answer

Down's syndrome

Answer

Klinefelter syndrome

Question 7

Which of the following childhood tumor uses N-myc gene amplification for its prognosis?

Accepted Answer

Neuroblastoma

Answer

Nephroblastoma

Answer

Retinoblastoma

Answer

Rhabdomyosarcoma

Question 8

A 25-year-old woman with amenorrhea has never had menarche. On physical examination, she is 145 cm (4 ft 9 in) tall. She has a webbed neck, a broad chest, and widely spaced nipples. Strong pulses are palpable in the upper extremities, but there are only weak pulses in the lower extremities. On abdominal MR imaging, her ovaries are small, elongated, and tubular. Which of the following karyotypes is she most likely to have?

Accepted Answer

45, X/46, XX

Answer

47, XXX

Answer

47, XXY

Answer

46, X, X (fra)

Question 9

BRCA1 gene lies on chromosome

Accepted Answer

17

Answer

18

Answer

21

Answer

20

Question 10

Number of chromosomes in Klinefelter syndrome:

Accepted Answer

47

Answer

44

Answer

46

Answer

45

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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