Molecular Pathology Practice Questions

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.

Q: If a chromosome divides along an axis perpendicular to its usual axis of division, what will it form?

Isochromosome. ### Explanation **Correct Answer: B. Isochromosome** **Mechanism:** Normally, during cell division (anaphase), a chromosome divides **longitudinally** (parallel to its long axis), separating the two sister chromatids. An **isochromosome** is formed when the centromere divides **transversely** (perpendicular to the usual axis). This abnormal division results in one daughter chromosome consisting of two short arms (p) and the other consisting of two long arms (q). Consequently, an isochromosome is a structural abnormality where one arm is lost and the other is duplicated, leading to partial monosomy and partial trisomy. **Analysis of Incorrect Options:** * **A. Ring chromosome:** Formed when a chromosome sustains breaks at both ends (telomeres), followed by the fusion of the remaining "sticky" ends into a circular shape. * **C. Acrocentric chromosome:** This refers to the normal morphology of chromosomes (like 13, 14, 15, 21, and 22) where the centromere is located very close to one end, resulting in one very short arm. * **D. Subtelocentric chromosome:** A descriptive term for a chromosome where the centromere is located between the midpoint and the tip (similar to submetacentric). **High-Yield Clinical Pearls for NEET-PG:** * **Most Common Isochromosome:** The most frequent isochromosome involves the long arm of the X chromosome: **i(Xq)**. * **Clinical Correlation:** i(Xq) is seen in approximately 15-20% of cases of **Turner Syndrome** (45,X/46,X,i(Xq)). These patients present with classic features like short stature and streak ovaries. * **Oncology Link:** Isochromosome 12p—**i(12p)**—is a highly specific diagnostic marker for **Germ Cell Tumors** (e.g., seminomas).

Q: Which of the following findings is NOT typically seen in Marfan syndrome?

Hypospadias. Explanation: Marfan syndrome is an autosomal dominant connective tissue disorder caused by a mutation in the **FBN1 gene** on chromosome 15, which encodes **fibrillin-1**. This protein is a major component of extracellular matrix microfibrils. The clinical manifestations primarily involve the skeletal, ocular, and cardiovascular systems [1]. **Why Hypospadias is the Correct Answer:** Hypospadias is a congenital malformation of the male urethra where the opening is on the ventral surface of the penis. It is typically related to hormonal imbalances or localized developmental failures during embryogenesis. It is **not** a feature of connective tissue dysplasia and is not associated with Marfan syndrome. **Analysis of Incorrect Options:** * **Scoliosis:** Skeletal overgrowth is a hallmark of Marfan syndrome. Asymmetric growth of the ribs and vertebrae frequently leads to spinal deformities like scoliosis or kyphosis. * **Hyperlaxity:** Deficiency in fibrillin-1 leads to weakened connective tissue in joint capsules and ligaments, resulting in generalized joint hypermobility (measured by the Beighton score) [1]. * **Pes planus:** Also known as flat feet, this occurs due to laxity of the ligaments supporting the medial longitudinal arch of the foot. It is a common minor skeletal criterion in the Ghent nosology. **High-Yield Clinical Pearls for NEET-PG:** * **Cardiovascular:** The most common cause of death is **Aortic Root Dilatation** leading to dissection or rupture. Mitral Valve Prolapse (MVP) is also common. * **Ocular:** The classic finding is **Ectopia Lentis** (dislocation of the lens), typically occurring **upward and outward (Superotemporal)** [1]. * **Skeletal Signs:** Look for **Steinberg sign** (thumb sign) and **Walker-Murdoch sign** (wrist sign). * **Differential:** Homocystinuria presents similarly but features downward lens dislocation, intellectual disability, and a prothrombotic state.

Question 1

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 2

Which of the following is an autosomal dominant disorder?

Accepted Answer

Neurofibromatosis

Answer

G6PD deficiency

Answer

Hirschsprung's disease

Answer

Vitamin D resistant rickets

Question 3

Cystic fibrosis affects which of the following systems?

Accepted Answer

Endocrine

Answer

Respiratory

Answer

Hepatobiliary

Answer

Genitourinary

Question 4

If a chromosome divides along an axis perpendicular to its usual axis of division, what will it form?

Accepted Answer

Isochromosome

Answer

Ring chromosome

Answer

Acrocentric chromosome

Answer

Subtelocentric chromosome

Question 5

Which of the following findings is NOT typically seen in Marfan syndrome?

Accepted Answer

Hypospadias

Answer

Scoliosis

Answer

Hyperlaxity

Answer

Pes planus

Question 6

All of the following are chromosomal breakage syndromes except?

Accepted Answer

Ehlers-Danlos syndrome

Answer

Fanconi's anaemia

Answer

Bloom syndrome

Answer

Ataxia telangiectasia

Question 7

Which of the following conditions demonstrates autosomal dominant inheritance?

Accepted Answer

Marfan syndrome

Answer

Sickle cell anaemia

Answer

Thalassemia

Answer

Hereditary spherocytosis

Question 8

Inheritance pattern of Familial Hypercholesterolemia is:

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Answer

X-linked recessive

Question 9

Genomic imprinting results in which of the following syndromes?

Accepted Answer

Angelman syndrome

Answer

Ehlers-Danlos Syndrome

Answer

Turner Syndrome

Answer

Haw River syndrome

Question 10

What is the most common aneuploidy compatible with life?

Accepted Answer

Down syndrome

Answer

Turner syndrome

Answer

Klinefelter's syndrome

Answer

Patau syndrome

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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