Molecular Pathology Practice Questions

Q: What is the interpretation of the given pedigree chart?

Autosomal dominant. ***Autosomal dominant*** - The trait appears in **every generation**, indicated by affected individuals in the first, second, and third generations [1]. - Both males and females are affected relatively equally, and affected individuals transmit the trait to approximately half of their offspring, consistent with **vertical transmission** [1]. - **Male-to-male transmission** is present, which definitively rules out X-linked inheritance patterns [1]. *Incomplete penetrance* - This pattern would typically show some individuals who carry the disease-causing genotype but **do not express the phenotype** (unaffected). - In this pedigree, all individuals who are expected to express the trait based on the clear dominant pattern are indeed affected. *Autosomal recessive* - This mode of inheritance would typically show **skipped generations**, meaning affected individuals would often have unaffected parents who are carriers [1]. - In this chart, every affected individual has at least one affected parent, ruling out an autosomal recessive pattern [1]. X-linked dominant - In X-linked dominant inheritance, **no male-to-male transmission** would be observed, as fathers pass their X chromosome only to daughters. - The presence of affected males transmitting the trait to male offspring rules out this inheritance pattern. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 148-151.

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.

Question 1

All of the following are tests done for Turner mosaic screening except?

Accepted Answer

Serum FSH

Answer

Karyotype

Answer

FISH

Answer

Buccal smear

Question 2

What is the interpretation of the given pedigree chart?

Accepted Answer

Autosomal dominant

Answer

Incomplete penetrance

Answer

Autosomal recessive

Answer

X-linked dominant

Question 3

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 4

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 5

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 6

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 7

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 8

Barr body is NOT seen in:

Accepted Answer

Turner syndrome

Answer

Marfan's syndrome

Answer

Down's syndrome

Answer

Klinefelter syndrome

Question 9

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

Accepted Answer

Neuroblastoma

Answer

Nephroblastoma

Answer

Retinoblastoma

Answer

Rhabdomyosarcoma

Question 10

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)

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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