Molecular Pathology Practice Questions

Q: What is the chromosomal defect associated with Prader-Willi syndrome?

Chromosome 15. ***Chromosome 15*** - **Prader-Willi syndrome** is characterized by a deletion or other abnormality on the **paternal copy** of **chromosome 15q11-q13** [1]. - This specific region contains genes critical for normal development and function, whose altered expression due to the paternal origin causes the syndrome [1]. *Chromosome 5* - Abnormalities of chromosome 5 are associated with conditions like **Cri-du-chat syndrome**, which involves a deletion on the short arm (5p). - This is not linked to the characteristic symptoms of Prader-Willi syndrome. *Chromosome 10* - Defects on chromosome 10 are associated with various other genetic disorders, such as **multiple endocrine neoplasia type 2 (MEN 2)** or **Cowden syndrome**. - There is no established direct link between chromosome 10 abnormalities and Prader-Willi syndrome. *Chromosome 21* - **Trisomy 21** is the genetic defect responsible for **Down syndrome** (presence of an extra copy of chromosome 21) [2]. - While a common chromosomal abnormality, it presents with a distinct set of clinical features different from Prader-Willi syndrome [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 182-183. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 171-172.

Q: Which of the following conditions is characterized by the absence of Barr bodies?

Turner syndrome. ***Turner syndrome*** - Females with **Turner syndrome** have a 45,XO karyotype, meaning they have only one X chromosome. - Since a **Barr body** is formed from the inactivation of one X chromosome in normal females (46,XX), individuals with Turner syndrome have **no Barr bodies** due to the absence of a second X chromosome. *Klinefelter syndrome* - Individuals with **Klinefelter syndrome** typically have a 47,XXY karyotype, meaning they have two X chromosomes. - The presence of two X chromosomes leads to the formation of **one Barr body** (from inactivation of one of the two X chromosomes), making this option incorrect. *Down's syndrome* - **Down's syndrome** is caused by trisomy 21 (extra copy of chromosome 21), which is an autosomal abnormality. - The number of Barr bodies in individuals with Down's syndrome depends on their sex chromosome complement (normal pattern: 46,XX females have one Barr body, 46,XY males have none). *Marfan's syndrome* - **Marfan's syndrome** is an autosomal dominant disorder affecting connective tissue, caused by a mutation in the **FBN1 gene**. - This condition does not involve abnormalities in sex chromosomes, so the number of Barr bodies follows the normal pattern (one in 46,XX females, none in 46,XY males).

Q: Which gene is primarily associated with Cowden syndrome?

PTEN. ***PTEN*** - Cowden syndrome is an **autosomal dominant** inherited disorder caused by germline mutations in the **PTEN (phosphatase and tensin homolog) tumor suppressor gene**. - The PTEN gene plays a crucial role in cell growth, proliferation, and apoptosis, and its dysfunction leads to uncontrolled cell growth and the development of multiple **hamartomas** and increased cancer risk. *TP53* - Mutations in the **TP53 gene** are primarily associated with Li-Fraumeni syndrome, a different inherited cancer predisposition syndrome characterized by a high risk of various cancers including sarcomas, breast cancer, and adrenocortical carcinoma. - While both inherited cancer syndromes involve tumor suppressor gene mutations, the specific gene affected and the clinical presentation differ significantly. *RB1* - The **RB1 gene** is a tumor suppressor gene primarily associated with **retinoblastoma**, a rare childhood eye cancer, and an increased risk of other cancers like osteosarcoma. - It plays a critical role in cell cycle regulation, and its mutation leads to uncontrolled cell division in the retina and other tissues. *KRAS* - The **KRAS gene** is an oncogene, not a tumor suppressor gene, and its mutations are frequently found in various sporadic cancers, particularly **colorectal cancer**, pancreatic cancer, and lung cancer. - KRAS mutations lead to constitutive activation of signaling pathways that promote cell growth and survival, but they are not the primary genetic cause of inherited Cowden syndrome.

Q: Which genetic condition is considered the most lethal due to monosomy?

Autosomal monosomy. ***Autosomal monosomy*** - **Autosomal monosomy** is the most lethal form of monosomy because it involves the loss of an entire autosome, leading to a severe imbalance in gene dosage. [1] - The human body cannot typically survive with the loss of a whole autosome, resulting in early embryonic or fetal demise. [1] *Chromosomal monosomy* - This is a broader term that includes both **autosomal monosomy** and **sex chromosome monosomy**. - While many forms of chromosomal monosomy are lethal, **sex chromosome monosomy (e.g., Turner syndrome)** is survivable, making the general term "chromosomal monosomy" less specific for the *most lethal* condition. [1] *Autosomal trisomy* - **Autosomal trisomy** involves an extra copy of an autosome (e.g., Trisomy 21 for Down syndrome), which, while causing significant health issues, is generally less lethal than the complete loss of an autosome. [1] - Many individuals with autosomal trisomies can survive to birth and beyond, unlike most cases of autosomal monosomy. [1] *Chromosomal trisomy* - This refers to having an extra copy of any chromosome, including **autosomes** and **sex chromosomes**. - While conditions like **Trisomy 13 (Patau syndrome)** and **Trisomy 18 (Edwards syndrome)** are highly lethal, the presence of *extra* genetic material is typically less universally lethal than the *absence* of an entire autosome. [1] **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169.

Q: Structure of chromosomes is studied by?

G-banding. ***G-banding*** - G-banding is the most commonly used method for the **detailed examination of chromosomes**, allowing visualization of banding patterns [1][2]. - It facilitates the identification of **chromosomal abnormalities** and is essential in **cytogenetic studies** [1][2]. *Q-banding* - Q-banding reveals a different pattern that is primarily used for **detection of specific chromosome markers** but is less common than G-banding. - It is more useful for cases requiring **fluorescent bright bands** but not for overall structural analysis. *C-banding* - C-banding specifically highlights the **centromeric regions** of chromosomes, not the overall structure. - It is limited in scope compared to G-banding since it doesn't provide a complete picture of chromosome morphology. *Brd V-staining* - Brd V-staining focuses on specific **DNA regions** and is related to the **visualization of viral DNA** in infected cells rather than chromosome structure. - It does not offer insights into the **general structural characteristics** of chromosomes like G-banding does. **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.

Q: Which of the following are examples of trinucleotide repeat mutations?

All of the options. ***All of the options*** - **Fragile X syndrome**, **Friedreich ataxia**, and **Huntington's chorea** are all well-known examples of genetic disorders caused by trinucleotide repeat expansions [1]. - The mutations involve an abnormal increase in the number of repetitions of a specific three-nucleotide sequence in the DNA [1]. *Fragile X syndrome* - This condition is caused by an expansion of the **CGG repeat** in the **FMR1 gene** on the X chromosome [1]. - The expansion leads to hypermethylation and silencing of the gene, impairing the production of fragile X mental retardation protein [1]. *Friedreich ataxia* - This is an autosomal recessive neurodegenerative disorder caused by an expansion of the **GAA repeat** in an intron of the **frataxin gene (FXN)**. - The repeat expansion interferes with transcription, leading to reduced frataxin protein levels. *Huntington's chorea* - This is an autosomal dominant neurodegenerative disorder caused by an expansion of the **CAG repeat** in the **huntingtin gene (HTT)**. - The expanded polyglutamine tract in the huntingtin protein leads to protein misfolding and neuronal damage, particularly in the striatum [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 177-181.

Q: Which of the following is considered a good prognostic factor for neuroblastoma?

Trk-A expression present. ***Trk-A expression present*** - **High TrkA (NTRK1) expression** is a well-established **favorable prognostic marker** in neuroblastoma - Associated with younger age, lower stage disease, and better differentiation - Tumors with high TrkA expression tend to be less aggressive and may undergo **spontaneous regression** [1] - Reflects activation of neurotrophin signaling pathways that promote differentiation rather than proliferation *Presence of 1p deletion* - **1p deletion** is a **poor prognostic factor** in neuroblastoma - Associated with aggressive disease and worse outcomes - The **absence** (not presence) of 1p deletion would be favorable *MYCN amplification* - **MYCN amplification** is the **strongest adverse prognostic factor** in neuroblastoma [1] - Found in approximately 20-25% of cases - Associated with rapid tumor progression, advanced stage, and poor survival - Patients with MYCN amplification are classified as high-risk regardless of other factors *Age greater than 18 months at diagnosis* - **Age > 18 months** is a **poor prognostic factor** - Younger children (especially < 12-18 months) have significantly better outcomes - Age is a key component of neuroblastoma risk stratification systems - Older children tend to present with more advanced disease and have worse response to therapy **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of Infancy and Childhood, pp. 483-487.

Question 1

Which of the following statements about FISH (Fluorescence In Situ Hybridization) is false?

Accepted Answer

Requires DNA polymerase

Answer

Used to detect copy number variations

Answer

Used to detect balanced translocations

Answer

Requires fluorescent probes

Question 2

What is the chromosomal defect associated with Prader-Willi syndrome?

Accepted Answer

Chromosome 15

Answer

Chromosome 5

Answer

Chromosome 10

Answer

Chromosome 21

Question 3

Which of the following conditions is characterized by the absence of Barr bodies?

Accepted Answer

Turner syndrome

Answer

Klinefelter syndrome

Answer

Down's syndrome

Answer

Marfan's syndrome

Question 4

Diagnose the disorder by looking at the karyotype.

Accepted Answer

Down syndrome.

Answer

Patau syndrome.

Answer

Turner syndrome.

Answer

Klinefelter syndrome.

Question 5

Which gene is primarily associated with Cowden syndrome?

Accepted Answer

PTEN

Answer

RB1

Answer

KRAS

Answer

TP53

Question 6

Which of the following is a chromosomal instability syndrome?

Accepted Answer

Bloom syndrome

Answer

Fanconi anemia

Answer

Ataxia-telangiectasia

Answer

None of the options

Question 7

Which genetic condition is considered the most lethal due to monosomy?

Accepted Answer

Autosomal monosomy

Answer

Chromosomal monosomy

Answer

Autosomal trisomy

Answer

Chromosomal trisomy

Question 8

Structure of chromosomes is studied by?

Accepted Answer

G-banding

Answer

C-banding

Answer

Q-banding

Answer

BrdU staining

Question 9

Which of the following are examples of trinucleotide repeat mutations?

Accepted Answer

All of the options

Answer

Friedreich ataxia

Answer

Fragile X syndrome

Answer

Huntington's chorea

Question 10

Which of the following is considered a good prognostic factor for neuroblastoma?

Accepted Answer

Trk-A expression present

Answer

MYCN amplification

Answer

Age greater than 18 months at diagnosis

Answer

Presence of 1p deletion

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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