Molecular Pathology Practice Questions

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.

Q: What is the genetic abnormality in fragile X-syndrome?

Trinucleotide repeat disorder.. Fragile X Syndrome is the most common cause of inherited intellectual disability and the most common monogenic cause of autism. **Why Option A is correct:** The condition is a classic example of a **Trinucleotide Repeat Disorder** [1]. It is caused by the expansion of a **CGG repeat** in the 5' untranslated region of the **FMR1 gene** located on the X chromosome (Xq27.3) [1]. * **Normal:** 200 repeats. This expansion leads to hypermethylation of the promoter region, silencing the gene and resulting in a deficiency of the Fragile X Mental Retardation Protein (FMRP), which is essential for neural development. **Why other options are incorrect:** * **Option B (Point mutation):** While point mutations can occur in the FMR1 gene, they account for <1% of cases. The hallmark of the syndrome is the triplet expansion. * **Option C (Not inheritable):** This is incorrect; it follows an **X-linked dominant** inheritance pattern with variable expressivity and reduced penetrance in females. * **Option D (Deletion):** Large deletions of the FMR1 gene are rare causes. The primary mechanism is expansion, not loss of a chromosomal segment [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Anticipation:** The disease severity increases and age of onset decreases in successive generations (occurs during maternal meiosis). * **Clinical Triad:** Long face with a prominent jaw (prognathism), large everted ears, and **macro-orchidism** (post-pubertal). * **Cytogenetics:** When cells are cultured in a folate-deficient medium, the X chromosome shows a "fragile site" (breakage) at the distal end of the long arm. * **Diagnosis:** PCR (for small expansions) and **Southern Blot** (to confirm full mutations and methylation status).

Question 1

Cystic fibrosis affects which of the following systems?

Accepted Answer

Endocrine

Answer

Respiratory

Answer

Hepatobiliary

Answer

Genitourinary

Question 2

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 3

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

Accepted Answer

Hypospadias

Answer

Scoliosis

Answer

Hyperlaxity

Answer

Pes planus

Question 4

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 5

Which of the following conditions demonstrates autosomal dominant inheritance?

Accepted Answer

Marfan syndrome

Answer

Sickle cell anaemia

Answer

Thalassemia

Answer

Hereditary spherocytosis

Question 6

Inheritance pattern of Familial Hypercholesterolemia is:

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Answer

X-linked recessive

Question 7

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 8

What is the most common aneuploidy compatible with life?

Accepted Answer

Down syndrome

Answer

Turner syndrome

Answer

Klinefelter's syndrome

Answer

Patau syndrome

Question 9

What is the genetic abnormality in fragile X-syndrome?

Accepted Answer

Trinucleotide repeat disorder.

Answer

Point mutation

Answer

Not inheritable

Answer

Deletion

Question 10

Deletion of chromosome 11 is associated with which of the following conditions?

Accepted Answer

Wilms tumor

Answer

Neuroblastoma

Answer

Retinoblastoma

Answer

Osteosarcoma

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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