Molecular Pathology Practice Questions

Q: What is the rapid method for chromosome identification in intersex conditions?

FISH. **Explanation:** The identification of chromosomal sex is a critical step in the management of intersex conditions (Disorders of Sex Development). **Why FISH is the correct answer:** **Fluorescence In Situ Hybridization (FISH)** is the preferred rapid method because it uses fluorescently labeled DNA probes that bind to specific sequences on the X and Y chromosomes. It can be performed on **interphase nuclei** (non-dividing cells), meaning it does not require a time-consuming cell culture. Results are typically available within **24–48 hours**, making it ideal for urgent gender assignment or clinical decision-making in neonates [1]. [1] **Why the other options are incorrect:** * **Karyotyping:** While it is the "Gold Standard" for definitive diagnosis, it requires cells to be in metaphase [2]. This necessitates a cell culture that takes **7–14 days**, making it too slow for immediate rapid identification. * **PCR (Polymerase Chain Reaction):** Though very fast and sensitive for detecting specific genes (like the *SRY* gene), it does not provide a comprehensive view of chromosome morphology or mosaicism as effectively as FISH in a clinical setting for intersex. * **SSCP (Single Strand Conformation Polymorphism):** This is a technique used to detect small mutations or polymorphisms in DNA sequences, not for identifying whole chromosomes or numerical abnormalities. **High-Yield Clinical Pearls for NEET-PG:** * **Barr Body:** A condensed, inactive X chromosome found in females. The number of Barr bodies = (Total X chromosomes - 1). * **SRY Gene:** Located on the short arm of the Y chromosome (Yp11.3); its presence determines male sexual differentiation. * **Gold Standard for Aneuploidy:** Karyotyping remains the definitive test for Turner (45,XO) and Klinefelter (47,XXY) syndromes, though FISH is the fastest initial screen [1].

Q: The following karyotype is seen in which of the following syndromes?

Cri du chat syndrome. ***Cri du chat syndrome*** - Caused by **deletion of chromosome 5 short arm (5p deletion)**, showing characteristic karyotype finding of **46,XX,del(5p)** or **46,XY,del(5p)**. - Clinical features include distinctive **cat-like cry** in infancy, **intellectual disability**, **microcephaly**, and growth retardation. *Bloom syndrome* - Autosomal recessive disorder caused by mutations in **BLM gene** on chromosome 15, not involving chromosome 5 deletion. - Characterized by **growth retardation**, **sun-sensitive skin rash**, and increased **cancer predisposition**. *Fragile X-syndrome* - X-linked disorder caused by **CGG repeat expansion** in the **FMR1 gene** on X chromosome, not chromosome 5 abnormality. - Features include **intellectual disability**, **autism spectrum behaviors**, and characteristic **facial features** with large ears. *Angelman syndrome* - Caused by **deletion or mutation of UBE3A gene** on **chromosome 15q11-q13**, not chromosome 5 deletion. - Presents with **severe intellectual disability**, **happy demeanor**, **ataxic gait**, and **seizures**.

Q: Trinucleotide repeat expansion causes all of the following conditions EXCEPT:

Hereditary motor and sensory neuropathy. **Explanation:** The correct answer is **Hereditary motor and sensory neuropathy (HMSN)**, also known as **Charcot-Marie-Tooth (CMT) disease**. Unlike the other options, HMSN is primarily caused by **gene duplications, deletions, or point mutations**, rather than trinucleotide repeat expansions. The most common subtype, CMT1A, is caused by a 1.5 Mb **duplication** of the *PMP22* gene on chromosome 17. **Analysis of other options:** * **Friedreich Ataxia:** This is an autosomal recessive condition caused by a **GAA** repeat expansion in the *FXN* gene (encoding frataxin) on chromosome 9. * **Spinocerebellar Ataxia (SCA):** This is a heterogeneous group of inherited disorders that present with ataxia and are frequently caused by repeat expansions [1]. Most common types (SCA 1, 2, 3, 6, 7) are caused by **CAG** repeat expansions. * **Huntington Disease:** An autosomal dominant neurodegenerative disorder caused by a **CAG** repeat expansion in the *HTT* gene on chromosome 4 [1]. **Clinical Pearls for NEET-PG:** 1. **Anticipation:** This phenomenon (where the disease becomes more severe or has an earlier onset in successive generations) is a hallmark of trinucleotide repeat disorders. 2. **Location of Repeats:** * **Exonic (Coding):** Usually **CAG** repeats (e.g., Huntington’s, SCAs). * **Intronic/Non-coding:** E.g., **GAA** in Friedreich Ataxia or **CTG** in Myotonic Dystrophy. 3. **Fragile X Syndrome:** Caused by **CGG** repeats; it is the most common inherited cause of intellectual disability. 4. **CMT Presentation:** Look for "stork leg" appearance (distal muscle wasting), high-arched feet (pes cavus), and hammer toes.

Q: Which of the following is a polygenic disorder?

Ankylosing spondylitis. ### Explanation **Correct Answer: A. Ankylosing Spondylitis** **Concept:** Polygenic (or multifactorial) disorders result from the combined influence of multiple genes along with environmental factors [1]. Unlike Mendelian disorders, they do not follow a simple inheritance pattern. **Ankylosing Spondylitis (AS)** is a classic example. While it has a very strong genetic association with **HLA-B27** (Major Histocompatibility Complex), HLA-B27 accounts for only about 20-30% of the total genetic risk [2]. Other non-MHC genes (like *ERAP1*, *IL23R*) and environmental triggers are required for the disease to manifest [2]. **Analysis of Incorrect Options:** * **B. Huntington’s Disease:** This is a **Monogenic (Single-gene)** disorder [1] with an **Autosomal Dominant** inheritance pattern. It is caused by a triplet repeat expansion (CAG) in the *HTT* gene on chromosome 4. * **C. Fragile X Syndrome:** This is a **Monogenic** disorder with an **X-linked Dominant** inheritance pattern. * **D. Pendred Syndrome:** This is a **Monogenic** disorder with an **Autosomal Recessive** inheritance pattern. **High-Yield Clinical Pearls for NEET-PG:** * **Common Polygenic Disorders:** Diabetes Mellitus, Hypertension, Schizophrenia, Cleft lip/palate, and most autoimmune diseases (SLE, RA) [1]. * **HLA-B27 Association:** While 90% of AS patients are HLA-B27 positive, only 1–5% of HLA-B27 positive individuals actually develop AS, reinforcing its polygenic/multifactorial nature [2].

Question 1

What is the rapid method for chromosome identification in intersex conditions?

Accepted Answer

FISH

Answer

PCR

Answer

SSCP

Answer

Karyotyping

Question 2

What is true about Klinefelter syndrome?

Accepted Answer

XXY

Answer

XO

Answer

Testes are absent

Answer

Female hypogonadism

Question 3

The following karyotype is seen in which of the following syndromes?

Accepted Answer

Cri du chat syndrome

Answer

Bloom syndrome

Answer

Fragile X-syndrome

Answer

Angelman syndrome

Question 4

Mutation in the gene encoding Dystrophin is known to cause all the following except?

Accepted Answer

Hypertrophic cardiomyopathy

Answer

Duchenne muscular dystrophy

Answer

Becker muscular dystrophy

Answer

Dilated cardiomyopathy

Question 5

Trinucleotide repeat expansion causes all of the following conditions EXCEPT:

Accepted Answer

Hereditary motor and sensory neuropathy

Answer

Friedreich ataxia

Answer

Spinocerebellar ataxia

Answer

Huntington disease

Question 6

Which of the following is a true statement regarding autosomal dominant disorders?

Accepted Answer

New germ cell mutations can occur in older fathers.

Answer

They often present early in life.

Answer

Complete penetrance is common.

Answer

The disorder is usually only seen in one generation.

Question 7

Jumping genes (transposons) are primarily involved in which of the following biological processes?

Accepted Answer

Gene regulation

Answer

Chromosomal aberrations

Answer

Gene movement within a genome

Answer

Gene amplification

Question 8

What is the chromosomal abnormality associated with 100% recurrence of disease in Down's syndrome?

Accepted Answer

Trisomy 21 with translocation

Answer

Translocation of 15 and 21 chromosomes

Answer

Mosaic pattern

Answer

Non-disjunction

Question 9

Which of the following is not associated with Down syndrome?

Accepted Answer

Deletion of chromosome 21

Answer

Trisomy 21

Answer

Mosaicism for chromosome 21

Answer

Robertsonian translocation involving chromosome 21

Question 10

Which of the following is a polygenic disorder?

Accepted Answer

Ankylosing spondylitis

Answer

Huntington's disease

Answer

Fragile X syndrome

Answer

Pendred syndrome

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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