Molecular Pathology Practice Questions

Q: Which one of the following conditions is not autosomal recessive?

Neurofibromatosis. **Explanation:** The correct answer is **Neurofibromatosis**, as it follows an **Autosomal Dominant (AD)** inheritance pattern, whereas the other listed conditions are Autosomal Recessive (AR). **1. Why Neurofibromatosis is the correct answer:** Neurofibromatosis (both Type 1 and Type 2) is a classic example of an Autosomal Dominant disorder. * **NF1 (von Recklinghausen disease):** Caused by a mutation in the *NF1* gene on **Chromosome 17** (encodes Neurofibromin). * **NF2:** Caused by a mutation in the *NF2* gene on **Chromosome 22** (encodes Merlin). A key feature of NF is **100% penetrance** but **variable expressivity**, meaning everyone with the gene will show symptoms, but the severity varies widely. **2. Analysis of Incorrect Options (AR Disorders):** * **Cystic Fibrosis:** The most common lethal AR disorder in Caucasians, caused by a mutation in the *CFTR* gene on Chromosome 7. * **Wilson’s Disease:** An AR disorder of copper metabolism due to mutations in the *ATP7B* gene on Chromosome 13. * **Hemochromatosis:** Most commonly an AR disorder (HFE gene mutation on Chromosome 6) leading to iron overload. **3. NEET-PG High-Yield Clinical Pearls:** * **Mnemonic for AR:** "Most enzyme deficiencies are AR" (except Hunter syndrome and Fabry disease). * **Mnemonic for AD:** "Structural protein defects are usually AD" (e.g., Marfan, Achondroplasia, NF). * **NF1 Clinical Triad:** Café-au-lait spots, Lisch nodules (iris hamartomas), and Neurofibromas. * **NF2 Clinical Hallmark:** Bilateral Acoustic Neuromas (Vestibular Schwannomas) [1].

Q: List the odd one out among the following:

Trisomy 18 (Noonan syndrome). **Explanation:** The core concept of this question lies in identifying the correct association between chromosomal aneuploidies and their clinical eponyms. **Why Option A is the Correct Answer (The "Odd One Out"):** Option A is factually incorrect and represents a mismatch. **Trisomy 18** is clinically known as **Edwards syndrome**, not Noonan syndrome. **Noonan syndrome** is an autosomal dominant genetic disorder (often involving mutations in the *PTPN11* gene) characterized by short stature, heart defects (pulmonic stenosis), and webbed neck. It is often referred to as the "male version of Turner syndrome" but occurs in both sexes with a normal karyotype. **Analysis of Incorrect Options (Correct Associations):** * **Option B: Trisomy 21 (Down syndrome):** This is the most common autosomal trisomy [1]. Key features include Simian crease, mental retardation, and Brushfield spots [1]. * **Option C: Trisomy 18 (Edwards syndrome):** This is the second most common autosomal trisomy. Key features include "rocker-bottom" feet, clenched fists with overlapping fingers, and micrognathia. * **Option D: Trisomy 13 (Patau syndrome):** Characterized by midline defects such as holoprosencephaly, cleft lip/palate, and polydactyly. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Trisomies:** **P**atau (13 - **P**uberty age), **E**dwards (18 - **E**lection age), **D**own (21 - **D**rinking age). * **Maternal Screening:** In Down syndrome, HCG and Inhibin-A are **increased**, while AFP and Estriol are **decreased**. In Edwards syndrome, all four markers are typically decreased. * **Noonan vs. Turner:** Noonan syndrome presents with **Pulmonic Stenosis**, whereas Turner syndrome (45,XO) is associated with **Coarctation of the Aorta** [2].

Q: Which of the following is NOT a characteristic of Turner syndrome?

True hermaphrodism. **Explanation:** **Turner Syndrome (45,X)** is the most common sex chromosome abnormality in females, characterized by the complete or partial absence of one X chromosome [1]. **Why "True Hermaphroditism" is the correct answer:** True Hermaphroditism (now termed **Ovotesticular Disorder of Sex Development**) is defined by the presence of both ovarian and testicular tissue in the same individual. Turner syndrome patients, however, do not possess testicular tissue. Instead, they have **"streak ovaries"** (dysgenetic gonads) where follicles are absent and replaced by fibrous stroma [1]. They are phenotypically female but remain sexually infantile. **Why the other options are incorrect:** * **Short Stature:** This is the most consistent clinical feature of Turner syndrome, primarily due to the haploinsufficiency of the **SHOX gene** located on the short arm of the X chromosome [1]. * **Webbed Neck (Cystic Hygroma/Pterygium colli):** This results from lymphatic obstruction during fetal development. Other related features include a low posterior hairline and a broad "shield-shaped" chest [1]. * **Dysgenetic Gonads:** As mentioned, accelerated oocyte loss leads to fibrous "streak" ovaries, resulting in primary amenorrhea and infertility. **High-Yield Clinical Pearls for NEET-PG:** * **Karyotype:** 45,X is the most common (50%), but mosaics (e.g., 45,X/46,XX) and structural abnormalities (Isochromosome Xq) also occur [1]. * **Cardiac Associations:** Bicuspid aortic valve (most common) and Coarctation of the aorta (pre-ductal). * **Renal Association:** Horseshoe kidney. * **Biochemical Markers:** Elevated LH and FSH levels (Hypergonadotropic hypogonadism) due to lack of feedback inhibition from estrogen. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 175-177.

Q: Which of the following is NOT a single gene disorder?

William's syndrome. **Explanation:** The distinction between single-gene (monogenic) disorders and chromosomal microdeletion syndromes is a high-yield concept for NEET-PG [2]. **Why William’s Syndrome is the correct answer:** Unlike the other options, **William’s Syndrome** is not caused by a mutation in a single gene. It is a **microdeletion syndrome** caused by a contiguous gene deletion on the long arm of **chromosome 7 (7q11.23)** [2]. This deletion involves approximately 26–28 genes, including the *ELN* (elastin) gene. Because it involves the loss of multiple neighboring genes rather than a single point mutation or triplet repeat, it is classified as a chromosomal disorder. **Why the other options are incorrect:** * **Hemochromatosis (Option A):** An autosomal recessive single-gene disorder, most commonly due to a mutation in the **HFE gene** (C282Y or H63D). * **Cystic Fibrosis (Option B):** A classic autosomal recessive single-gene disorder caused by mutations in the **CFTR gene** on chromosome 7. * **Huntington’s Disease (Option D):** An autosomal dominant single-gene disorder caused by a **CAG trinucleotide repeat expansion** in the *HTT* gene on chromosome 4. **Clinical Pearls for NEET-PG:** * **William’s Syndrome Triad:** "Elfin" facies, Intellectual disability (with "cocktail party" personality/extreme loquacity), and Cardiovascular defects (most commonly **Supravalvular Aortic Stenosis**) [1]. * **Diagnosis:** The gold standard for detecting microdeletions like William’s is **FISH** (Fluorescence In Situ Hybridization) or Chromosomal Microarray [2]. * **Metabolic association:** Idiopathic **infantile hypercalcemia** is a characteristic feature of William’s syndrome.

Question 1

A normal parent has two siblings with osteogenesis imperfecta. What is the most likely pattern of inheritance?

Accepted Answer

Germline mosaicism

Answer

Mutation

Answer

Anticipation

Answer

Genomic imprinting

Question 2

Which one of the following conditions is not autosomal recessive?

Accepted Answer

Neurofibromatosis

Answer

Cystic fibrosis

Answer

Wilson's disease

Answer

Hemochromatosis

Question 3

What chromosomal reason can explain autosomal recessive disorders in a child when one parent is unaffected and the other is a carrier?

Accepted Answer

Uniparental disomy

Answer

Germline mosaicism

Answer

Genomic imprinting

Answer

Incomplete penetrance

Question 4

Chromosomal non-disjunction is responsible for all of the following conditions EXCEPT:

Accepted Answer

Neurofibromatosis type 1

Answer

Down's syndrome

Answer

Prader-Willi syndrome

Answer

Angelman syndrome

Question 5

List the odd one out among the following:

Accepted Answer

Trisomy 18 (Noonan syndrome)

Answer

Trisomy 21 (Down syndrome)

Answer

Trisomy 18 (Edwards syndrome)

Answer

Trisomy 13 (Patau syndrome)

Question 6

Which of the following is NOT a characteristic of Turner syndrome?

Accepted Answer

True hermaphrodism

Answer

Short stature

Answer

Webbed neck

Answer

Dysgenetic gonads

Question 7

Which of the following features is not characteristic of Fragile X syndrome?

Accepted Answer

Micro-orchidism

Answer

Hyperextensible joints

Answer

Small nose

Answer

Mental retardation

Question 8

Which of the following is NOT a single gene disorder?

Accepted Answer

William's syndrome

Answer

Hemochromatosis

Answer

Cystic fibrosis

Answer

Huntington's disease

Question 9

Which of the following is NOT an X-linked disorder?

Accepted Answer

Cystic fibrosis

Answer

Hemophilia A

Answer

Duchenne muscular dystrophy

Answer

Fragile X syndrome

Question 10

BRAF V600E mutations are seen in all of the following except?

Accepted Answer

Grade II astrocytoma

Answer

Langerhans cell histiocytosis

Answer

Erdheim Chester disease

Answer

Ovarian carcinoma

Molecular Pathology — MCQs

Molecular Pathology — MCQs

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