Molecular Pathology Practice Questions

Q: A patient's karyotype shows the following. What clinical abnormality is expected?

Rockerbottom feet. ***Rockerbottom feet*** - **Trisomy 18 (Edwards syndrome)** characteristically presents with **rockerbottom feet** (convex-shaped soles) as a key diagnostic feature. - Other typical findings include **clenched fists with overlapping fingers**, **micrognathia**, and **ventricular septal defects**. *Gynecomastia with long thin limbs* - This combination is characteristic of **Klinefelter syndrome (47,XXY)**, not Trisomy 18. - **Klinefelter syndrome** presents with **tall stature**, **gynecomastia**, and **hypogonadism** in males. *Short stature with polydactyly* - **Polydactyly** (extra digits) is a hallmark feature of **Trisomy 13 (Patau syndrome)**, not Trisomy 18. - **Trisomy 13** also presents with **holoprosencephaly**, **cleft lip/palate**, and **microphthalmia**. *Webbed neck with widely spaced nipples* - These features are characteristic of **Turner syndrome (45,X)**, affecting females exclusively. - **Turner syndrome** also presents with **short stature**, **lymphedema**, and **coarctation of aorta**.

Q: A specific karyotype is observed in a female patient. Which of the following syndromes is associated with this karyotype?

Cri du chat syndrome. ***Cri du chat syndrome*** - Associated with a **deletion of the short arm of chromosome 5 (5p-)**, which is clearly visible on **karyotype analysis** as 46,XX,del(5p). - Characterized by a distinctive **high-pitched cry** resembling a cat's meow, along with **intellectual disability** and **microcephaly**. *Bloom syndrome* - Caused by mutations in the **BLM gene** on chromosome 15, diagnosed through **molecular genetic testing**, not karyotype. - Features include **growth retardation**, **sun-sensitive skin rash**, and increased risk of **malignancies**. *Fragile X syndrome* - Results from **CGG repeat expansion** in the **FMR1 gene** on the X chromosome, requiring **molecular analysis** for diagnosis. - Karyotype may show a **fragile site** on Xq27.3, but this is not reliably detected in standard karyotyping. *Angelman syndrome* - Caused by **deletion or mutation of UBE3A gene** on chromosome 15q11-q13, diagnosed by **methylation studies** or molecular testing. - Karyotype is typically **normal** unless there's a large deletion, which occurs in only 10-15% of cases.

Q: What is the trinucleotide repeat seen in Fragile X syndrome?

CGG. **Explanation:** **Fragile X Syndrome** is the most common inherited cause of intellectual disability and is characterized by a trinucleotide repeat expansion in the **FMR1 gene** located on the X chromosome [1]. 1. **Correct Option (A) CGG:** The expansion occurs in the 5' untranslated region of the FMR1 gene. Normal individuals have 6–50 repeats. In Fragile X, this expands to a "full mutation" of **>200 CGG repeats**, leading to hypermethylation of the promoter, gene silencing, and a deficiency of the Fragile X Mental Retardation Protein (FMRP) [1]. 2. **Incorrect Option (B) CTG:** This repeat is associated with **Myotonic Dystrophy** (Type 1). 3. **Incorrect Option (C) CAG:** This is the most common repeat in polyglutamine diseases, most notably **Huntington’s Disease** and Spinocerebellar Ataxias [1]. 4. **Incorrect Option (D) GAA:** This repeat is seen in the frataxin gene in **Friedreich’s Ataxia**. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Triad:** Intellectual disability, large everted ears, and **macro-orchidism** (post-pubertal). * **Cytogenetics:** When cells are cultured in folate-deficient medium, the X chromosome shows a "fragile site" (breakage) at the distal long arm (Xq27.3) [2]. * **Anticipation:** The disease shows "anticipation," where the severity increases or age of onset decreases in successive generations due to further expansion of the repeats during oogenesis. * **Premutation (55–200 repeats):** Associated with Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) and Premature Ovarian Failure [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 177-181. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 186-187.

Q: Klinefelter syndrome is diagnosed by?

Karyotyping. **Explanation:** **Klinefelter syndrome (47, XXY)** is a chromosomal aneuploidy characterized by the presence of one or more extra X chromosomes in a male phenotype. 1. **Why Karyotyping is the Correct Answer:** Karyotyping is the **gold standard** for diagnosing chromosomal abnormalities. It involves visualizing the complete set of chromosomes in a cell (usually from peripheral blood lymphocytes) during metaphase. In Klinefelter syndrome, karyotyping reveals the classic **47, XXY** pattern (or mosaics like 46, XY/47, XXY), confirming the numerical chromosomal aberration that defines the disorder. 2. **Why Other Options are Incorrect:** * **USG Abdomen:** While it may be used to look for undescended testes or assess pelvic structures, it cannot identify the genetic cause. * **Triple Test:** This is a prenatal screening tool (measuring AFP, hCG, and estriol) used to assess the risk of Down syndrome or neural tube defects; it is not diagnostic for Klinefelter syndrome. * **Echocardiography:** Used to detect structural heart defects (like Mitral Valve Prolapse, which can occur in Klinefelter), but it is a supportive investigation, not a diagnostic one. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Features:** Tall stature, gynecomastia, small firm testes (testicular dysgenesis), and infertility (azoospermia). * **Biochemical Profile:** Hypergonadotropic hypogonadism (↑ FSH, ↑ LH, ↓ Testosterone) due to Leydig cell dysfunction and seminiferous tubule hyalinization. * **Barr Body:** Positive (unlike normal males) due to the extra X chromosome. * **Risk:** Increased risk of male breast cancer and extragonadal germ cell tumors.

Q: What is the name of this chromosomal abnormality?

Ring chromosome. ***Ring chromosome*** - A **ring chromosome** forms when both **telomeric ends** of a chromosome break and fuse together, creating a **circular structure** that appears ring-shaped on karyotype. - Often associated with **loss of genetic material** at the breakpoints, leading to various developmental abnormalities and **growth retardation**. *Translocation* - Involves the **transfer of a chromosome segment** from one chromosome to another, not forming a circular structure. - Appears as **abnormal banding patterns** between two different chromosomes on karyotype, not a ring shape. *Telomeric fusion* - Refers to the **fusion of telomeres** from different chromosomes, typically resulting in **dicentric chromosomes** or chromosome bridges. - Does not create a **ring-shaped structure** but rather abnormal linear chromosome configurations. *Isochromosome* - Forms when a chromosome divides **transversely through the centromere** instead of longitudinally, creating two identical arms. - Results in a **symmetrical chromosome** with duplicated arms (e.g., i(17q)), not a circular ring structure.

Question 1

Which of the following genetic aberrations is not a causative mechanism in cases of Prader-Willi syndrome?

Accepted Answer

Single nucleotide polymorphisms (SNPs)

Answer

Gene deletions

Answer

Defective genomic imprinting

Answer

Uniparental disomy

Question 2

A patient's karyotype shows the following. What clinical abnormality is expected?

Accepted Answer

Rockerbottom feet

Answer

Gynecomastia with long thin limbs

Answer

Short stature with polydactyly

Answer

Webbed neck with widely spaced nipples

Question 3

A specific karyotype is observed in a female patient. Which of the following syndromes is associated with this karyotype?

Accepted Answer

Cri du chat syndrome

Answer

Bloom syndrome

Answer

Fragile X syndrome

Answer

Angelman syndrome

Question 4

Karyotyping can be used to diagnose which of the following diseases?

Accepted Answer

Klinefelter’s syndrome

Answer

Multiple myeloma

Answer

Niemann-Pick disease

Answer

Pemphigus

Question 5

What is the trinucleotide repeat seen in Fragile X syndrome?

Accepted Answer

CGG

Answer

CTG

Answer

CAG

Answer

GAA

Question 6

Which of the following statements is true regarding ataxia telangiectasia?

Accepted Answer

Increase in Alpha-fetoprotein (AFP)

Answer

Increases the risk of squamous cell carcinoma

Answer

Inherited in an autosomal dominant pattern

Answer

None of the above

Question 7

Klinefelter syndrome is diagnosed by?

Accepted Answer

Karyotyping

Answer

USG abdomen

Answer

Triple test

Answer

Echocardiography

Question 8

22q11 deletion leading to Di George syndrome is associated with which of the following?

Accepted Answer

Hypocalcemia

Answer

Hypokalemia

Answer

Hyperkalemia

Answer

Hypercalcemia

Question 9

In a family, the father has widely spaced eyes, increased facial hair, and deafness. One of the three children has deafness with similar facial features. The mother is normal. Which one of the following patterns of inheritance is least likely in this case?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Answer

X-linked recessive

Question 10

What is the name of this chromosomal abnormality?

Accepted Answer

Ring chromosome

Answer

Translocation

Answer

Telomeric fusion

Answer

Isochromosome

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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