Genetic Disorders and Biochemical Pathology Practice Questions

Q: Which of the following is a marker for neural tube defects?

↑Acetylcholinesterase. ***↑Acetylcholinesterase*** - Elevated **acetylcholinesterase (AChE)** in amniotic fluid is a highly specific marker for **open neural tube defects (NTDs)**. - AChE is normally confined to nervous tissue; its presence in amniotic fluid suggests leakage from exposed fetal neural tissue. - AChE provides higher **specificity** than AFP for confirming open NTDs. *↑Alkaline phosphatase* - Elevated **alkaline phosphatase (ALP)** in amniotic fluid is associated with abnormalities like **omphalocele** and **gastroschisis**, but not specifically NTDs. - ALP levels can also be elevated in other conditions and are not a primary marker for neural tube defects. *↑Pseudocholinesterase* - **Pseudocholinesterase (butyrylcholinesterase)** is found in the liver, plasma, and other tissues, and its elevation is not a specific marker for neural tube defects. - It is sometimes used as a marker for liver function or exposure to certain toxins, not for fetal malformations. *↑Alpha-fetoprotein (AFP)* - While **AFP** is elevated in maternal serum and amniotic fluid with open NTDs, it is a **screening marker** with lower specificity. - AFP elevation can occur in other conditions (abdominal wall defects, multiple gestation, fetal demise), making it less specific than acetylcholinesterase for confirming NTDs.

Q: Tuberous sclerosis caused by mutations in TSC2 gene encodes which of the following proteins?

Tuberin. ***Tuberin*** - The **TSC2 gene** codes for the protein **tuberin**, which forms a complex with hamartin (encoded by TSC1). - This **tuberin-hamartin complex** functions as a tumor suppressor by negatively regulating the mTOR pathway. *Hamartin* - **Hamartin** is encoded by the **TSC1 gene**, not TSC2. - While it forms a complex with tuberin (TSC2 gene product), it is a distinct protein. *Merlin* - **Merlin** is a protein encoded by the **NF2 gene**, which is associated with **Neurofibromatosis type 2 (NF2)**, not tuberous sclerosis. - It plays a role in cell growth regulation and cell-cell adhesion. *Ankyrin* - **Ankyrin** proteins are a family of adapter proteins that link integral membrane proteins to the spectrin-actin cytoskeleton. - They are involved in many cellular processes but are **not directly encoded by the TSC2 gene** nor are they primarily associated with tuberous sclerosis.

Q: What is the underlying defect in Ataxia telangiectasia?

Double-strand DNA break repair. ***ds DNA break repair*** - Ataxia telangiectasia is primarily caused by a defect in the **ATM gene**, which plays a critical role in **double-strand DNA break repair** [1]. - Patients often present with **ataxia**, **telangiectasia**, and an increased risk of **cancers** due to impaired DNA repair mechanisms [1]. *Nucleotide Excision repair* - This pathway is responsible for repairing **DNA damage** caused by UV light and chemical exposure, which is not the defect in ataxia telangiectasia. - Disorders like **xeroderma pigmentosum** stem from defects in this pathway [1], not ataxia telangiectasia. *Mismatch repair* - Mismatch repair is important for correcting errors that occur during **DNA replication**, leading to conditions like **Lynch syndrome** when defective. - Ataxia telangiectasia is not associated with errors in this process, thus making it an incorrect option. *Base Excision Repair* - This repair mechanism handles small-scale DNA damage, especially from oxidative stress, which does not relate to ataxia telangiectasia pathology. - Conditions like **familial adenomatous polyposis** are associated with base excision repair defects, highlighting the difference. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 322-323.

Q: Refsum's disease is due to deficiency of which of the following enzyme?

Phytanic alpha oxidase. ***Phytanic alpha oxidase*** - **Refsum's disease** is an **autosomal recessive peroxisomal disorder** characterized by the accumulation of **phytanic acid**. - This accumulation occurs due to the deficiency of **phytanic acid alpha-oxidase**, an enzyme crucial for the **alpha-oxidation** of branched-chain fatty acids. *Malonate dehydrogenase* - This enzyme is involved in the metabolism of **malonate**, typically oxidizing it to **malonyl-CoA**. - Its deficiency is not associated with Refsum's disease or the accumulation of phytanic acid. *Thiophorase* - Also known as **succinyl-CoA:3-ketoacid CoA transferase**, thiophorase is involved in **ketone body metabolism**. - Its deficiency leads to **succinyl-CoA:3-ketoacid CoA transferase deficiency**, causing **ketoacidosis**, not Refsum's disease. *Succinate thiokinase* - Also known as **succinyl-CoA synthetase**, this enzyme plays a role in the **Krebs cycle**, converting **succinyl-CoA to succinate**. - Its deficiency is a rare metabolic disorder presenting with **encephalopathy and lactic acidosis**, unrelated to phytanic acid metabolism.

Q: Inheritance associated with fragile X syndrome is-

X-linked dominant. ***X-linked dominant*** - Fragile X syndrome is caused by a **trinucleotide repeat expansion** (CGG) in the **FMR1 gene** located on the X chromosome. - The inheritance pattern is **X-linked dominant with reduced penetrance** and variable expressivity. - Males are typically more severely affected due to having only one X chromosome (hemizygous state). - **Importantly, carrier females are often affected** - approximately 50% show mild to moderate intellectual disability, anxiety, or social difficulties, which distinguishes it from X-linked recessive inheritance. - The condition shows **genetic anticipation** - repeat expansions increase in successive generations, particularly through maternal transmission. *X-linked recessive inheritance* - In true X-linked recessive disorders (like hemophilia A), carrier females are typically asymptomatic. - Fragile X syndrome does not fit this pattern because **carrier females frequently manifest symptoms**, making it dominant rather than recessive. - If it were recessive, heterozygous females would be unaffected carriers. *Autosomal dominant inheritance* - This pattern involves genes on autosomes (non-sex chromosomes) affecting males and females equally. - Fragile X syndrome is **X-linked**, not autosomal - the FMR1 gene is located on the X chromosome. - The sex-linked nature explains the higher prevalence and severity in males. *Autosomal recessive inheritance* - This pattern requires two copies of a mutated gene on autosomes, with both parents typically being carriers. - Fragile X syndrome is **X-linked**, not autosomal, and shows sex-specific inheritance patterns. - The pattern of inheritance through the X chromosome rules out any autosomal pattern.

Q: Trinucleotide sequence associated with spinocerebellar ataxia is?

CAG. ***CAG*** - The **CAG trinucleotide repeat** is associated with **most forms of spinocerebellar ataxia (SCA)**, including SCA1, SCA2, SCA3 (Machado-Joseph disease), SCA6, SCA7, and SCA17. - An expansion of this repeat leads to an elongated **polyglutamine tract** in the affected protein, causing protein misfolding and neuronal dysfunction. - CAG is the **most common** trinucleotide repeat expansion associated with SCA. *CUG* - **CUG repeats** are primarily associated with **myotonic dystrophy type 1**. - While CUG expansions are found in **SCA8**, CAG repeats are far more commonly associated with the majority of spinocerebellar ataxias. - The expansion of CUG repeats in the **3' untranslated region** causes RNA-mediated toxicity. *GGC* - **GGC repeats** are not a common trinucleotide expansion associated with classic spinocerebellar ataxia. - While other repeat expansions exist in various genetic disorders, GGC is not the primary repeat linked to SCA. *CGG* - **CGG trinucleotide repeat** expansions are characteristic of **Fragile X syndrome**, a common cause of inherited intellectual disability. - This repeat expansion occurs in the FMR1 gene and is not the primary repeat associated with spinocerebellar ataxia.

Q: Acute intermittent porphyria is associated with which type of inheritance?

Autosomal dominant. ***Autosomal dominant*** - **Acute intermittent porphyria (AIP)** is inherited in an **autosomal dominant** pattern, meaning only one copy of the mutated gene (HMBS gene) is sufficient to cause the disorder. - This inheritance pattern leads to a 50% chance of passing the condition to each offspring from an affected parent. - **Important clinical feature:** AIP demonstrates **incomplete penetrance** (10-20%), meaning many individuals with the mutation never develop clinical symptoms, which is why family history may appear negative despite autosomal dominant inheritance. *Autosomal recessive* - **Autosomal recessive** disorders require two copies of the mutated gene (one from each parent) for the disease to manifest. - This pattern is characteristic of conditions like cystic fibrosis or sickle cell anemia, not acute intermittent porphyria. *X-linked dominant* - **X-linked dominant** inheritance involves a gene located on the X chromosome, where a single copy of the mutated gene is sufficient for disease expression in both males and females. - This pattern is typically seen in conditions such as fragile X syndrome or Rett syndrome, with distinct inheritance patterns differing from AIP. *X-linked recessive* - **X-linked recessive** disorders, such as hemophilia or Duchenne muscular dystrophy, primarily affect males as they only have one X chromosome. - Females are typically carriers but can be affected if they inherit two mutated X chromosomes, a pattern not seen in acute intermittent porphyria.

Q: Which chromosome contains the gene responsible for MEN2 (Multiple Endocrine Neoplasia type 2)?

10q11.2. ***10q11.2*** - The **MEN2 gene** is located on **chromosome 10** at band **q11.2**. - Mutations in this gene, specifically the **RET proto-oncogene**, are responsible for Multiple Endocrine Neoplasia type 2. *11q13* - This chromosomal location is associated with the **MEN1 gene**, which causes Multiple Endocrine Neoplasia type 1. - MEN1 involves tumors of the **parathyroid**, **pancreatic islet cells**, and **anterior pituitary**. *13q11* - This location is not typically associated with the **MEN genes** or other well-known multiple endocrine neoplasia syndromes. - It is more commonly linked to other genetic disorders or specific gene loci unrelated to **endocrine tumor syndromes**. *11q10.2* - This is an incorrect or imprecisely described chromosomal location in the context of Multiple Endocrine Neoplasia syndromes. - While **chromosome 11** is relevant for **MEN1**, the specific band **11q10.2** is not the correct location for either MEN1 or MEN2 genes.

Q: Match the enzyme with the disease caused due to its deficiency: **Enzymes:** 1. Fumarylacetoacetate hydrolase 2. Tyrosine transaminase 3. Tyrosinase 4. Homogentisate oxidase **Diseases:** A. Tyrosinemia Type I B. Tyrosinemia Type II C. Albinism D. Alkaptonuria

1 → A, 2 → B, 3 → C, 4 → D. **1 → A, 2 → B, 3 → C, 4 → D** - **Fumarylacetoacetate hydrolase** deficiency causes **Tyrosinemia Type I**, a severe metabolic disorder affecting the liver and kidneys with accumulation of toxic metabolites like succinylacetone. - **Tyrosine transaminase** deficiency leads to **Tyrosinemia Type II** (Richner-Hanhart syndrome), characterized by ocular and cutaneous lesions with elevated plasma tyrosine. - **Tyrosinase** deficiency results in **Albinism** (oculocutaneous albinism type 1), due to lack of melanin production from tyrosine. - **Homogentisate oxidase** deficiency causes **Alkaptonuria**, where homogentisic acid accumulates, turning urine black upon standing and causing ochronosis. *1 → A, 2 → C, 3 → D, 4 → B* - This incorrectly matches tyrosine transaminase with Albinism and tyrosinase with Alkaptonuria, reversing the melanin synthesis pathway enzyme with the tyrosine degradation pathway enzyme. *1 → C, 2 → D, 3 → A, 4 → B* - This incorrectly matches fumarylacetoacetate hydrolase with Albinism (which requires tyrosinase deficiency) and homogentisate oxidase with Tyrosinemia Type II (which requires tyrosine transaminase deficiency). *1 → C, 2 → A, 3 → D, 4 → B* - This incorrectly places the severe hepatorenal disease (Tyrosinemia Type I) with tyrosine transaminase instead of fumarylacetoacetate hydrolase, and mismatches the melanin pathway enzyme with alkaptonuria.

Q: Which of the following chromosomes is classified as a Group D chromosome?

Chromosome 15. ***Chromosome 15*** - **Group D chromosomes** are characterized by their **medium size** and **acrocentric structure**, meaning the centromere is located very close to one end. - Chromosome 15 fits this description along with chromosomes 13 and 14. *Chromosome 3* - This is a **large metacentric chromosome**, meaning its centromere is located in the middle, and it belongs to **Group A**. - Its size and centromere position differentiate it from the acrocentric chromosomes of Group D. *Chromosome 6* - Chromosome 6 is a **medium-sized submetacentric chromosome**, with its centromere slightly off-center, placing it within **Group C**. - This group distinguishes itself from the acrocentric chromosomes of Group D. *Chromosome 12* - Chromosome 12 is also categorized as a **medium-sized submetacentric chromosome**, belonging to **Group C**. - Its centromere position is not near the telomere, unlike the acrocentric chromosomes of Group D.

Question 1

Which of the following is a marker for neural tube defects?

Accepted Answer

↑Acetylcholinesterase

Answer

↑Pseudocholinesterase

Answer

↑Alpha-fetoprotein (AFP)

Answer

↑Alkaline phosphatase

Question 2

Tuberous sclerosis caused by mutations in TSC2 gene encodes which of the following proteins?

Accepted Answer

Tuberin

Answer

Hamartin

Answer

Merlin

Answer

Ankyrin

Question 3

What is the underlying defect in Ataxia telangiectasia?

Accepted Answer

Double-strand DNA break repair

Answer

Nucleotide Excision Repair

Answer

Mismatch Repair

Answer

Base Excision Repair

Question 4

Refsum's disease is due to deficiency of which of the following enzyme?

Accepted Answer

Phytanic alpha oxidase

Answer

Thiophorase

Answer

Succinate thiokinase

Answer

Malonate dehydrogenase

Question 5

Inheritance associated with fragile X syndrome is-

Accepted Answer

X-linked dominant

Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked recessive

Question 6

Trinucleotide sequence associated with spinocerebellar ataxia is?

Accepted Answer

CAG

Answer

CUG

Answer

GGC

Answer

CGG

Question 7

Acute intermittent porphyria is associated with which type of inheritance?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Answer

X-linked recessive

Question 8

Which chromosome contains the gene responsible for MEN2 (Multiple Endocrine Neoplasia type 2)?

Accepted Answer

10q11.2

Answer

13q11

Answer

11q13

Answer

11q10.2

Question 9

Match the enzyme with the disease caused due to its deficiency:

**Enzymes:**
1. Fumarylacetoacetate hydrolase
2. Tyrosine transaminase
3. Tyrosinase
4. Homogentisate oxidase

**Diseases:**
A. Tyrosinemia Type I
B. Tyrosinemia Type II
C. Albinism
D. Alkaptonuria

Accepted Answer

1 → A, 2 → B, 3 → C, 4 → D

Answer

1 → A, 2 → C, 3 → D, 4 → B

Answer

1 → C, 2 → D, 3 → A, 4 → B

Answer

1 → C, 2 → A, 3 → D, 4 → B

Question 10

Which of the following chromosomes is classified as a Group D chromosome?

Accepted Answer

Chromosome 15

Answer

Chromosome 3

Answer

Chromosome 6

Answer

Chromosome 12

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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