Molecular Pathology Practice Questions

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].

Q: Which of the following is an autosomal dominant disorder?

Neurofibromatosis. **Explanation:** **Neurofibromatosis (Option B)** is the correct answer. Both Type 1 (NF1) and Type 2 (NF2) are classic examples of **autosomal dominant** disorders. NF1 is caused by a mutation in the *NF1* gene on chromosome 17 (encoding neurofibromin), while NF2 involves the *NF2* gene on chromosome 22 (encoding merlin). These conditions exhibit high penetrance but variable expressivity, meaning clinical severity can vary significantly among affected individuals. **Analysis of Incorrect Options:** * **A. G6PD Deficiency:** This is an **X-linked recessive** disorder. It is the most common enzyme deficiency worldwide, leading to episodic hemolytic anemia under oxidative stress (e.g., fava beans, primaquine). * **C. Hirschsprung's Disease:** This is primarily a **polygenic/multifactorial** disorder, though it can sometimes be associated with specific genetic syndromes (like Down syndrome) or mutations in the *RET* proto-oncogene. It does not follow a simple autosomal dominant inheritance pattern. * **D. Vitamin D Resistant Rickets (Hereditary Hypophosphatemic Rickets):** This is the classic example of an **X-linked dominant** disorder. It is characterized by renal phosphate wasting and is one of the few X-linked dominant conditions frequently tested in exams. **High-Yield Clinical Pearls for NEET-PG:** * **NF1 Clinical Triad:** Café-au-lait spots, Lisch nodules (iris hamartomas), and neurofibromas. * **Mnemonic for Autosomal Dominant Disorders:** "Very Powerful DOMINANT" (Von Willebrand, Polycystic Kidney Disease, Dystrophia Myotonica, Osteogenesis Imperfecta, Marfan, Intermittent Porphyria, **Neurofibromatosis**, Achondroplasia, Noonan, Tuberous Sclerosis). * **Genetic Concept:** NF1 has one of the highest mutation rates in the human genome; approximately 50% of cases arise from *de novo* mutations.

Question 1

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 2

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 3

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 4

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 5

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 6

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 7

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 8

Which of the following is a polygenic disorder?

Accepted Answer

Ankylosing spondylitis

Answer

Huntington's disease

Answer

Fragile X syndrome

Answer

Pendred syndrome

Question 9

BRCA1 and BRCA2 genes are located on which chromosomes?

Accepted Answer

Chromosome 13 and 17

Answer

Chromosome 17 and 13

Answer

Chromosome 11 and 13

Answer

Chromosome 13 and 11

Question 10

Which of the following is an autosomal dominant disorder?

Accepted Answer

Neurofibromatosis

Answer

G6PD deficiency

Answer

Hirschsprung's disease

Answer

Vitamin D resistant rickets

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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