Molecular Pathology Practice Questions

Q: A Barr body is absent in which of the following conditions?

Turner syndrome. ### Explanation **1. Understanding Barr Bodies (The Lyon Hypothesis)** A Barr body is an inactivated X chromosome found in the somatic cells of females [1]. According to the Lyon hypothesis, in individuals with more than one X chromosome, all X chromosomes except one are inactivated to ensure dosage compensation. The number of Barr bodies is calculated using the formula: **Number of Barr bodies = (Total number of X chromosomes – 1).** **2. Why Turner Syndrome is the Correct Answer** * **Turner Syndrome (45, XO):** These individuals have only one X chromosome [1]. Applying the formula (1 – 1 = 0), they have **zero Barr bodies**. Since a Barr body represents an inactivated "extra" X chromosome, its absence is a hallmark of this condition. **3. Analysis of Incorrect Options** * **Klinefelter Syndrome (47, XXY):** Although phenotypically male, these individuals possess two X chromosomes [1]. One X chromosome undergoes inactivation, resulting in **one Barr body** (2 – 1 = 1). * **Super Female Syndrome (47, XXX):** These individuals have three X chromosomes. Two X chromosomes are inactivated, resulting in **two Barr bodies** (3 – 1 = 2). **4. NEET-PG High-Yield Clinical Pearls** * **Specimen Collection:** Barr bodies are most commonly demonstrated in **buccal mucosal smears** or "drumsticks" in polymorphonuclear leukocytes (neutrophils). * **Lyonization:** This process occurs early in embryonic life (around the blastocyst stage) and is random, fixed, and incomplete (some genes on the inactive X remain active) [1]. * **Rule of Thumb:** If the question asks for the number of Barr bodies, simply subtract 1 from the total number of X chromosomes present in the karyotype. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 173-175.

Q: Defective chromosome associated with DiGeorge syndrome is -

22. **Explanation:** **1. Why Option D (Chromosome 22) is Correct:** DiGeorge Syndrome (DGS) is caused by a microdeletion on the **long arm (q) of chromosome 22**, specifically at the **22q11.2** locus. This region contains the *TBX1* gene, which is critical for the normal development of the **3rd and 4th pharyngeal pouches**. Failure of these pouches to develop leads to the classic triad of thymic hypoplasia (T-cell deficiency), parathyroid hypoplasia (hypocalcemia), and conotruncal cardiac defects. **2. Why Other Options are Incorrect:** * **Option A (Chromosome 7):** Associated with **Williams Syndrome** (deletion at 7q11.23), characterized by "elfin" facies, hypercalcemia, and supravalvular aortic stenosis. * **Option B (Chromosome 15):** Associated with **Prader-Willi Syndrome** (paternal deletion) and **Angelman Syndrome** (maternal deletion) at the 15q11-q13 locus. * **Option C (Chromosome 17):** Associated with **Neurofibromatosis Type 1 (NF1)** and **Miller-Dieker Syndrome** (lissencephaly). **3. High-Yield Clinical Pearls for NEET-PG:** * **CATCH-22 Mnemonic:** **C**ardiac defects (Truncus arteriosus, TOF), **A**bnormal facies, **T**hymic aplasia, **C**left palate, **H**ypocalcemia/Hypoparathyroidism, due to **22**q11 deletion. * **Diagnosis:** The gold standard for detecting this microdeletion is **FISH** (Fluorescence In Situ Hybridization). * **Velocardiofacial Syndrome:** This is a related spectrum disorder also caused by the 22q11.2 deletion, primarily featuring cleft palate and cardiac defects. * **Biochemical Hallmark:** Refractory neonatal seizures due to **hypocalcemia** (secondary to absent parathyroid glands).

Q: Mitochondrial chromosomal abnormality leads to which of the following conditions?

Lebers hereditary optic neuropathy. **Explanation:** **Leber’s Hereditary Optic Neuropathy (LHON)** is the correct answer because it is a classic example of a disorder caused by **mitochondrial DNA (mtDNA) mutations** [1]. Since mitochondria are inherited exclusively from the oocyte, LHON follows a **maternal inheritance pattern** (all children of an affected mother are at risk, but affected fathers do not pass it to their offspring). Pathophysiologically, mutations in mtDNA genes (encoding subunits of NADH dehydrogenase) lead to defective oxidative phosphorylation, causing selective degeneration of retinal ganglion cells and subsequent bilateral central vision loss. **Analysis of Incorrect Options:** * **Angelman Syndrome & Prader-Willi Syndrome:** These are examples of **Genomic Imprinting** (epigenetic regulation) involving chromosome 15 [1]. Angelman results from the loss of the maternal allele (UBE3A gene), while Prader-Willi results from the loss of the paternal allele. * **Myotonic Dystrophy:** This is a **Trinucleotide Repeat Disorder** (CTG repeat in the DMPK gene) [1]. It follows an Autosomal Dominant pattern and exhibits "anticipation." **High-Yield Clinical Pearls for NEET-PG:** * **Mitochondrial DNA (mtDNA):** It is circular, double-stranded, and lacks histones. It has a higher mutation rate than nuclear DNA. * **Heteroplasmy:** This term refers to the coexistence of wild-type and mutated mtDNA within a single cell [1]. The severity of mitochondrial diseases depends on the proportion of mutated mtDNA (Threshold effect) [1]. * **Other Mitochondrial Diseases:** MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) and MERRF (Myoclonic Epilepsy with Ragged Red Fibers). * **Histology:** "Ragged Red Fibers" on Gomori trichrome stain are a hallmark of mitochondrial myopathies. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 177, 181.

Q: FBN1 gene mutation is seen in which of the following genetic disorders?

Marfan syndrome. ***Marfan syndrome***- The **FBN1 gene** (located on chromosome 15) encodes the protein **fibrillin-1**, a major component of the extracellular matrix, deficiency of which leads to the clinical manifestations of Marfan syndrome.- **Fibrillin-1** is integral to the formation of elastic fibers; its defect causes issues in the skeletal, ocular, and cardiovascular systems [1].*Ehlers-Danlos syndrome*- This group of disorders is primarily caused by defects in **collagen synthesis** (e.g., **COL5A1**, **COL3A1**) or processing, leading to joint hypermobility and skin hyperextensibility [2].- It is not typically associated with the **FBN1** mutation.*Homocystinuria*- This disorder is an autosomal recessive metabolic error usually caused by a deficiency of the enzyme **cystathionine beta-synthase** (CBS) [3].- It involves abnormal metabolism of **methionine** and **cysteine**, leading to high levels of **homocysteine**, and is not linked to **FBN1**.*von Hippel-Lindau syndrome*- This is a predisposition syndrome caused by a mutation in the **VHL tumor suppressor gene** (located on chromosome 3).- It predisposes patients to various tumors, including **hemangioblastomas** and **renal cell carcinoma**, and has no association with **FBN1**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 153-154. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 155-156. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 150-151.

Q: A 25-year-old man presents with headaches, visual disturbances, and hypertension. MRI brain shows a cerebellar hemangioblastoma, and abdominal imaging reveals multiple cysts in the kidneys along with a solid renal mass suggestive of renal cell carcinoma. His father had similar findings and died from a brain tumor in his 40s. Which of the following chromosomal abnormalities is most likely associated with his condition?

Deletion on chromosome 3p. ***Deletion on chromosome 3p*** - This clinical presentation of **cerebellar hemangioblastoma**, **renal cell carcinoma (clear cell type)**, and multiple renal and pancreatic cysts in a familial context is highly characteristic of **Von Hippel-Lindau (VHL) disease**. [1] - VHL disease is caused by an inherited or sporadic inactivation (deletion or mutation) of the **VHL tumor suppressor gene** located on the short arm of chromosome 3 (**3p25.3**). [2] *Deletion on chromosome 13q* - Deletion of the **RB1 gene** on chromosome 13q is associated with **retinoblastoma** and an increased risk of **osteosarcoma**, not VHL disease. - The clinical picture of headaches, cerebellar mass, and renal cell carcinoma is distinct from the typical presentation of RB1-associated disorders. *Deletion on chromosome 17p* - Deletion or mutation of the **TP53 gene** on chromosome 17p is primarily associated with **Li-Fraumeni syndrome**, which increases the risk for a variety of cancers, including sarcomas, breast cancer, and adrenocortical carcinoma, but less commonly VHL-related tumors. - This deletion is not the genetic locus for the VHL tumor suppressor gene. *Trisomy of chromosome 12* - Trisomy 12 is a common chromosomal anomaly found in B-cell chronic lymphocytic leukemia (**CLL**) and some benign tumors like **uterine leiomyomas**. - It is an inappropriate anomaly for a familial syndrome presenting with hemangioblastoma and renal cell carcinoma. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Manifestations Of Central And Peripheral Nervous System Disease, pp. 724-725. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Kidney, pp. 958-959.

Q: A child presents with a right transverse palmar crease, a cardiac defect, survival into childhood, and mild intellectual impairment. What chromosomal mechanism is most likely associated with these findings?

Mosaicism. ***Mosaicism*** - **Mosaicism** is the presence of two or more cell lines with different genetic constitutions in a single individual, allowing for a **milder phenotype** of chromosomal syndromes like Trisomy 21. - The combination of classic Down syndrome features (transverse palmar crease, cardiac defect) with relatively **mild intellectual impairment** and survival into childhood with better outcomes suggests **Mosaic Down Syndrome** (mosaic Trisomy 21). - In mosaicism, only a proportion of cells carry the extra chromosome 21, resulting in **less severe manifestations** compared to complete trisomy. *Incorrect: Trisomy* - While **complete Trisomy 21** (Down syndrome) presents with similar features, it typically causes **more severe intellectual disability** and greater phenotypic expression. - The emphasis on **"mild" intellectual impairment** in this case points toward mosaicism rather than complete trisomy. *Incorrect: Haploid* - **Haploid** refers to a cell having only one set of chromosomes (n=23), a state that is **incompatible with human survival** beyond early embryonic development. - A complete haploid individual cannot survive into **childhood**. *Incorrect: Monosomy* - **Monosomy** (loss of one chromosome, 2n-1) for autosomes is typically **lethal in utero**, making survival into childhood impossible. - The only viable monosomy is **Monosomy X** (Turner syndrome), which presents with distinct features (short stature, webbed neck, ovarian dysgenesis) without the characteristic Down syndrome features described.

Q: A child presents with micrognathia and low-set ears. These clinical features are commonly associated with which type of genetic abnormality?

Deletion. ***Correct: Deletion*** - **Micrognathia** and **low-set ears** are characteristic features of many syndromes caused by chromosomal deletions, such as **DiGeorge syndrome** (22q11.2 deletion) or **Cri-du-chat syndrome** (5p deletion). - The loss of a significant segment of a chromosome leads to **haploinsufficiency** for multiple genes, severely impacting craniofacial and auricular development. *Incorrect: Translocation* - This involves the exchange of segments between non-homologous chromosomes; while it can cause genetic disorders, it is not the most common genetic mechanism leading to the specific classic combination of micrognathia and low-set ears. - **Balanced translocations** usually do not cause clinical symptoms in the carrier, but can lead to abnormal gametes and offspring with partial monosomy or trisomy. *Incorrect: Amplification* - This refers to the increase in the copy number of a gene or DNA sequence, which is primarily linked to cancer development (**oncogenesis**, e.g., *HER2* amplification), not generalized congenital dysmorphism. - While large segmental duplications (a form of gain) can cause syndromes, specific amplification events are rarely the cause of micrognathia or low-set ears. *Incorrect: Inversion* - This involves a chromosomal segment reversing its orientation; the primary concern is the formation of **unbalanced gametes** during meiosis, particularly with **pericentric inversions**. - Although offspring can inherit unbalanced chromosomes resulting in abnormalities, deletions remain the most common cause for the specific constellation of features mentioned.

Question 1

A Barr body is absent in which of the following conditions?

Accepted Answer

Turner syndrome

Answer

Klinefelter syndrome

Answer

Super female syndrome (Triple X syndrome)

Answer

None of the above

Question 2

Defective chromosome associated with DiGeorge syndrome is -

Accepted Answer

22

Answer

7

Answer

15

Answer

17

Question 3

The most likely inheritance pattern depicted in the following pedigree is:

Accepted Answer

X-linked dominant

Answer

Autosomal dominant

Answer

X-linked recessive

Answer

Autosomal recessive

Question 4

Mitochondrial chromosomal abnormality leads to which of the following conditions?

Accepted Answer

Lebers hereditary optic neuropathy

Answer

Angelman syndrome

Answer

Prader Willi syndrome

Answer

Myotonic dystrophy

Question 5

What is true about autosomal dominant inheritance?

Accepted Answer

50% affected, if one parent is affected.

Answer

25% affected and 50% carrier, if one parent is affected.

Answer

50% affected and 75% carrier, if both parents are affected.

Answer

75% affected, if both parents are affected.

Question 6

A trait in which the parents are clinically normal and only siblings are affected, with males and females affected in equal proportions, is characteristic of which inheritance pattern?

Accepted Answer

Autosomal Recessive (AR)

Answer

Autosomal Dominant (AD)

Answer

X-linked Dominant (XLD)

Answer

X-linked Recessive (XLR)

Question 7

FBN1 gene mutation is seen in which of the following genetic disorders?

Accepted Answer

Marfan syndrome

Answer

Homocystinuria

Answer

von Hippel-Lindau syndrome

Answer

Ehlers-Danlos syndrome

Question 8

A 25-year-old man presents with headaches, visual disturbances, and hypertension. MRI brain shows a cerebellar hemangioblastoma, and abdominal imaging reveals multiple cysts in the kidneys along with a solid renal mass suggestive of renal cell carcinoma. His father had similar findings and died from a brain tumor in his 40s. Which of the following chromosomal abnormalities is most likely associated with his condition?

Accepted Answer

Deletion on chromosome 3p

Answer

Trisomy of chromosome 12

Answer

Deletion on chromosome 17p

Answer

Deletion on chromosome 13q

Question 9

A child presents with a right transverse palmar crease, a cardiac defect, survival into childhood, and mild intellectual impairment. What chromosomal mechanism is most likely associated with these findings?

Accepted Answer

Mosaicism

Answer

Haploid

Answer

Monosomy

Answer

Trisomy

Question 10

A child presents with micrognathia and low-set ears. These clinical features are commonly associated with which type of genetic abnormality?

Accepted Answer

Deletion

Answer

Amplification

Answer

Inversion

Answer

Translocation

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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