Molecular Pathology Practice Questions

Q: Which of the following chromosomal abnormalities is indicated by the chromosomal mapping?

Klinefelter syndrome. ***Klinefelter syndrome*** - The karyotype **47,XXY** shows an extra X chromosome in males, which is the classic chromosomal pattern for Klinefelter syndrome. - Clinical features include **hypogonadism**, **tall stature**, **gynecomastia**, and **infertility** due to the additional X chromosome. *Cri du chat syndrome* - Caused by a **deletion on chromosome 5p** (5p-), not an extra sex chromosome as shown in the mapping. - Characterized by a distinctive **cat-like cry**, **microcephaly**, and **intellectual disability**. *Eagle's syndrome* - This is **not a chromosomal abnormality** but rather an anatomical condition involving elongated **styloid process** or calcified **stylohyoid ligament**. - Presents with **throat pain**, **dysphagia**, and **otalgia**, unrelated to karyotypic changes. *Down's syndrome* - Results from **trisomy 21** (47,XX+21 or 47,XY+21), showing an extra chromosome 21, not extra sex chromosomes. - Clinical features include **intellectual disability**, **characteristic facial features**, and **cardiac defects**.

Q: In the provided karyotype, which abnormality is observed? The karyotype shows 2 X-chromosomes and 1 Y-chromosome.

Gynecomastia with long thin limbs. ***Gynecomastia with long thin limbs*** - The karyotype **47,XXY** indicates **Klinefelter syndrome**, which commonly presents with **gynecomastia** due to hormonal imbalances and **eunuchoid body habitus** with long limbs. - Males with Klinefelter syndrome typically have **tall stature**, **sparse body hair**, and **small testes** along with these characteristic physical features. *Short stature with polydactyly* - Short stature with polydactyly is characteristic of **Patau syndrome (trisomy 13)** with karyotype **47,XX/XY,+13**. - This syndrome also presents with **cleft lip/palate**, **microcephaly**, and **cardiac defects**, not associated with the XXY karyotype. *Loose connective tissue at the nape of the neck* - **Webbed neck** or nuchal fold is a classic feature of **Turner syndrome** with karyotype **45,X**. - Turner syndrome affects females and includes **short stature**, **streak gonads**, and **coarctation of aorta**, unlike Klinefelter syndrome. *High-pitched crying* - **High-pitched cat-like cry** is pathognomonic for **Cri-du-chat syndrome** caused by **deletion of chromosome 5p**. - This syndrome presents with **microcephaly**, **intellectual disability**, and **distinctive facial features**, not related to sex chromosome abnormalities.

Q: All of the following have autosomal dominant pattern of inheritance except?

Hemophilia A. The correct answer is **Hemophilia A** because it follows an **X-linked recessive (XLR)** pattern of inheritance, not autosomal dominant. 1. **Hemophilia A (Option B):** This is caused by a deficiency of Factor VIII. The gene is located on the X chromosome [2]. Therefore, it primarily affects males, while females are typically asymptomatic carriers. A father cannot pass the disease to his son, which is a hallmark of X-linked inheritance. 2. **Huntington’s Chorea (Option A):** This is a classic **Autosomal Dominant (AD)** neurodegenerative disorder caused by CAG trinucleotide repeats on Chromosome 4. It exhibits "anticipation," where the disease manifests earlier in successive generations. 3. **Tuberous Sclerosis (Option C):** This is an **AD** neurocutaneous syndrome (phakomatosis) caused by mutations in the *TSC1* (hamartin) or *TSC2* (tuberin) genes. It is characterized by the development of benign tumors (hamartomas) in multiple organs. 4. **Marfan’s Syndrome (Option D):** This is an **AD** connective tissue disorder caused by a mutation in the *FBN1* gene on Chromosome 15 [1], leading to defective fibrillin-1. **NEET-PG High-Yield Pearls:** * **Mnemonic for AD disorders:** "**V**ery **P**owerful **M**nemonic **H**elps **A**ll **D**octors" (**V**on Willebrand, **P**olycystic Kidney, **M**arfan/**M**yotonic dystrophy, **H**untington/**H**ereditary Spherocytosis, **A**chondroplasia, **D**ystrophia Myotonica). * **Hemophilia A vs. B:** Both are XLR. Hemophilia A = Factor VIII deficiency; Hemophilia B (Christmas Disease) = Factor IX deficiency [2]. * **Vertical Transmission:** AD disorders typically show vertical transmission (seen in every generation), whereas XLR disorders often skip generations via carrier females.

Q: What is the abnormality seen in the following karyotype?

Gynecomastia with long thin limbs. ***Gynecomastia with long thin limbs*** - The karyotype 47,XXY represents **Klinefelter syndrome**, which classically presents with **gynecomastia** due to hormonal imbalances and testosterone deficiency. - Patients typically exhibit **tall stature** with **long limbs** and **eunuchoid body proportions** due to delayed epiphyseal closure. *Short stature with webbed neck* - These features are characteristic of **Turner syndrome** with karyotype **45,X** (monosomy X). - Turner syndrome also presents with **shield chest**, **coarctation of aorta**, and **streak ovaries**. *High-pitched cry* - This is the hallmark feature of **Cri du chat syndrome** caused by **deletion of chromosome 5p**. - Associated with **microcephaly**, **intellectual disability**, and **distinctive facial features**. *Round face with protruding tongue* - These are classic features of **Down syndrome** (trisomy 21) with karyotype **47,XX+21** or **47,XY+21**. - Down syndrome also presents with **intellectual disability**, **simian crease**, and **cardiac defects**.

Q: AKT1 E17K somatic mutation is associated with which of the following carcinomas?

Breast carcinoma. **Explanation:** The **AKT1 E17K** mutation is a specific somatic point mutation occurring in the pleckstrin homology domain of the AKT1 protein. This mutation results in the constitutive localization of AKT1 to the plasma membrane, leading to the permanent activation of the **PI3K/AKT/mTOR pathway**, which promotes cell survival, growth, and proliferation. **1. Why Breast Carcinoma is correct:** The AKT1 E17K mutation is most frequently identified in **Breast Carcinoma**, specifically in **Estrogen Receptor-positive (ER+)** and **ductal** subtypes. It occurs in approximately 2–5% of breast cancers. It is often mutually exclusive with PIK3CA mutations, suggesting they serve redundant roles in activating the same oncogenic pathway. **2. Analysis of Incorrect Options:** * **Gastric Carcinoma:** While the PI3K pathway is often altered in gastric cancer, it is usually via *PIK3CA* mutations or *PTEN* loss, rather than the specific AKT1 E17K mutation. * **Ovarian Carcinoma:** AKT2 amplification is more common in ovarian cancer. AKT1 mutations are rare in this site. * **Pancreatic Carcinoma:** The hallmark mutation in pancreatic cancer is *KRAS* (found in >90% of cases), not AKT1. **High-Yield Clinical Pearls for NEET-PG:** * **AKT1 E17K** is a "gain-of-function" mutation. * **PI3K/AKT/mTOR Pathway:** This is a major target for newer "targeted therapies" (e.g., Alpelisib for PIK3CA). * **Mutual Exclusivity:** In breast cancer, AKT1 mutations, PIK3CA mutations, and PTEN loss rarely occur in the same tumor. * **Other associations:** Besides breast cancer, AKT1 E17K is also notably found in **Proteus Syndrome** (a mosaic genetic disorder) and some cases of endometrial cancer.

Q: The NF-2 gene codes for which protein?

Merlin. The **NF-2 gene**, located on **chromosome 22q12**, is a tumor suppressor gene. It encodes a protein called **Merlin** (also known as Schwannomin). Merlin is structurally related to the ERM (Ezrin-Radixin-Moesin) family of proteins. Its primary function is to link cell-surface glycoproteins to the actin cytoskeleton. When Merlin is lost, cells lose contact inhibition, leading to uncontrolled proliferation and tumor formation. [1] **Analysis of Options:** * **Option C (Merlin):** Correct. Merlin acts as a tumor suppressor by facilitating contact inhibition through the Hippo signaling pathway. [1] * **Option B (Neurofibromin):** Incorrect. This protein is encoded by the **NF-1 gene** located on chromosome 17. Neurofibromin acts as a GTPase-activating protein (GAP) that downregulates the RAS signaling pathway. [1] * **Options A & D (Catenins):** Incorrect. Catenins (α and β) are proteins that interact with E-cadherin to maintain cell-cell adhesion. While β-catenin is involved in the WNT signaling pathway (mutated in APC/Colon cancer), it is not the product of the NF-2 gene. **High-Yield Clinical Pearls for NEET-PG:** * **Clinical Presentation:** NF-2 is classically associated with **Bilateral Acoustic Neuromas** (Vestibular Schwannomas). Remember the mnemonic: **NF-2** = **2** ears (Bilateral acoustic neuromas) on chromosome **22**. [1] * **MISME Syndrome:** NF-2 is characterized by **M**ultiple **I**nherited **S**chwannomas, **M**eningiomas, and **E**pendymomas. [2] * **Ocular Sign:** Juvenile posterior subcapsular lenticular opacities (cataracts) are a common early diagnostic sign of NF-2. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1248-1249. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1319-1320.

Q: This gene mapping indicates:

Down’s syndrome. ***Down's syndrome*** - The gene mapping/karyotype shows **trisomy 21** (47,XY+21 or 47,XX+21), which is the characteristic chromosomal abnormality for Down's syndrome. - This extra chromosome 21 causes the classic features including **intellectual disability**, **characteristic facial features**, and increased risk of **congenital heart defects**. *Klinefelter syndrome* - Caused by **XXY karyotype** (47,XXY), not trisomy 21 as shown in the gene mapping. - Presents with **hypogonadism**, **tall stature**, and **infertility** in males, not the features associated with chromosome 21. *Cri du chat syndrome* - Results from **deletion of chromosome 5p** (5p- syndrome), not an extra chromosome 21. - Characterized by a distinctive **high-pitched cry**, **microcephaly**, and **severe intellectual disability**. *Eagle's syndrome* - This is **not a chromosomal disorder** and would not be identified through gene mapping or karyotype analysis. - It's an anatomical condition involving **elongated styloid process** causing throat and neck pain, unrelated to genetic abnormalities.

Question 1

Which of the following chromosomal abnormalities is indicated by the chromosomal mapping?

Accepted Answer

Klinefelter syndrome

Answer

Cri du chat syndrome

Answer

Eagle’s syndrome

Answer

Down’s syndrome

Question 2

Hereditary retinoblastomas develop due to an abnormality in which of the following chromosomes?

Accepted Answer

13q14

Answer

13p14

Answer

14p13

Answer

14q13

Question 3

In the provided karyotype, which abnormality is observed? The karyotype shows 2 X-chromosomes and 1 Y-chromosome.

Accepted Answer

Gynecomastia with long thin limbs

Answer

Short stature with polydactyly

Answer

Loose connective tissue at the nape of the neck

Answer

High-pitched crying

Question 4

All of the following have autosomal dominant pattern of inheritance except?

Accepted Answer

Hemophilia A

Answer

Huntington's chorea

Answer

Tuberous sclerosis

Answer

Marfan's syndrome

Question 5

What is the abnormality seen in the following karyotype?

Accepted Answer

Gynecomastia with long thin limbs

Answer

Short stature with webbed neck

Answer

High-pitched cry

Answer

Round face with protruding tongue

Question 6

AKT1 E17K somatic mutation is associated with which of the following carcinomas?

Accepted Answer

Breast carcinoma

Answer

Gastric carcinoma

Answer

Ovarian carcinoma

Answer

Pancreatic carcinoma

Question 7

Which of the following is NOT true about chromosomal instability syndromes?

Accepted Answer

Autosomal dominant inheritance

Answer

DNA repair defect

Answer

Increased risk of malignancy

Answer

Associated immunodeficiency

Question 8

The NF-2 gene codes for which protein?

Accepted Answer

Merlin

Answer

α Catenin

Answer

Neurofibromin

Answer

α β Catenin

Question 9

This gene mapping indicates:

Accepted Answer

Down’s syndrome

Answer

Klinefelter syndrome

Answer

Cri du chat syndrome

Answer

Eagle’s syndrome

Question 10

Defective DNA repair is seen in which of the following conditions?

Accepted Answer

Ataxia telangiectasia

Answer

Tuberous sclerosis

Answer

Von Hippel Lindau disease

Answer

Neurofibromatosis 1

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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