Genetic Disorders and Biochemical Pathology Practice Questions

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: 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: 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: Inheritance associated with congenital adrenal hyperplasia -

AR. ***AR*** - Congenital adrenal hyperplasia (CAH) typically results from deficiencies in enzymes involved in adrenal steroid synthesis, most commonly **21-hydroxylase deficiency**. - These enzyme deficiencies are inherited in an **autosomal recessive (AR)** pattern, meaning an individual must inherit two copies of the defective gene (one from each parent) to manifest the condition. *AD* - **Autosomal dominant (AD)** inheritance means only one copy of a defective gene is needed for the condition to appear. This is not the typical inheritance pattern for CAH. - While some rare forms of adrenal disorders can be AD, the classic presentation of CAH is not. *XR* - **X-linked recessive (XR)** inheritance refers to conditions caused by genes on the X chromosome, primarily affecting males. CAH does not follow this pattern. - Males are generally more severely affected than females in XR disorders, which is not the case for common forms of CAH. *XD* - **X-linked dominant (XD)** inheritance means a single copy of a defective gene on the X chromosome can cause the disorder. This pattern is not characteristic of CAH. - XD disorders often have different presentations in males and females, and CAH does not fit this genetic model.

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: What is the most definitive method for confirming 46,XY disorders of sexual development?

Genetic testing. ***Genetic testing*** - Genetic testing, such as **karyotyping** and **DNA sequencing**, can identify abnormalities in genes responsible for male sexual development, confirming 46,XY DSD. - This method directly pinpoints the underlying genetic cause, providing a **definitive diagnosis** for specific DSDs like **androgen insensitivity syndrome** or **5-alpha-reductase deficiency**. - Molecular analysis can detect mutations in genes like **SRY, AR, SRD5A2**, and other genes involved in sex determination and differentiation. *USG abdomen* - **Ultrasonography** of the abdomen can visualize internal reproductive organs and identify anatomical abnormalities, but it does not reveal the underlying genetic cause. - While useful for assessing morphology, it is an **imaging modality** and not a definitive diagnostic tool for genetic conditions. *Hormonal study* - **Hormonal studies** measure levels of androgens, estrogens, and other related hormones, which can indicate impaired hormone production or action. - While essential for understanding the **physiological impact** of DSDs, hormonal studies provide indirect evidence and do not definitively identify the genetic origin. *Gonadal biopsy* - **Histopathological examination** of gonadal tissue can reveal tissue architecture and cell types, which may support the diagnosis. - However, it is an **invasive procedure** and does not identify the specific genetic mutation responsible for the DSD, making it less definitive than genetic testing.

Q: Pendred syndrome is caused by a mutation in which gene?

SLC26A4 gene. ***SLC26A4 gene*** - Pendred syndrome is an autosomal recessive disorder characterized by **sensorineural hearing loss** and **goiter**, caused by mutations in the *SLC26A4 gene*. - The *SLC26A4 gene* encodes pendrin, a **chloride-iodide transporter** found in the inner ear and thyroid gland, crucial for endolymph production and iodide transport. *Bartillin* - The *BSND gene* encodes bartillin, which is associated with **Bartter syndrome type IV**, characterized by renal salt wasting, deafness, and metabolic alkalosis. - While it involves deafness, it's distinct from Pendred syndrome as it doesn't primarily involve thyroid dysfunction. *Fibrillin* - **Fibrillin-1** is encoded by the *FBN1 gene* and mutations in this gene cause **Marfan syndrome**, a genetic disorder affecting connective tissue, leading to cardiovascular, skeletal, and ocular abnormalities. - It is not associated with hearing loss or thyroid issues, as seen in Pendred syndrome. *Reticulin* - Reticulin refers to a type of collagen fiber (primarily **collagen type III**) found in connective tissues. - Mutations directly related to the protein "reticulin" are not known to cause specific genetic syndromes like Pendred syndrome.

Q: Gene responsible for Wilson disease is situated on which chromosome?

Chromosome 13. ***Chromosome 13*** - The **ATP7B gene**, responsible for Wilson disease, is located on **chromosome 13** (specifically 13q14.3). - Mutations in this gene lead to impaired copper transport and accumulation in various organs, particularly the liver and brain. *Chromosome 11* - This chromosome is associated with various genetic disorders, such as **sickle cell disease** (HBB gene) and **Beckwith-Wiedemann syndrome**. - Wilson disease is not associated with genes on this chromosome. *Chromosome 12* - **Phenylketonuria (PKU)** (PAH gene) and some forms of **Noonan syndrome** are linked to genes on chromosome 12. - Wilson disease is not associated with genes on this chromosome. *Chromosome 14* - This chromosome contains genes associated with **Alpha-1 antitrypsin deficiency** and some forms of **Alzheimer's disease**. - It does not contain the ATP7B gene responsible for Wilson disease.

Question 1

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

Accepted Answer

Tuberin

Answer

Hamartin

Answer

Merlin

Answer

Ankyrin

Question 2

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 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

Inheritance associated with congenital adrenal hyperplasia -

Accepted Answer

AR

Answer

AD

Answer

XR

Answer

XD

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

What is the most definitive method for confirming 46,XY disorders of sexual development?

Accepted Answer

Genetic testing

Answer

USG abdomen

Answer

Hormonal study

Answer

Gonadal biopsy

Question 9

Pendred syndrome is caused by a mutation in which gene?

Accepted Answer

SLC26A4 gene

Answer

Fibrillin

Answer

Bartillin

Answer

Reticulin

Question 10

Gene responsible for Wilson disease is situated on which chromosome?

Accepted Answer

Chromosome 13

Answer

Chromosome 11

Answer

Chromosome 12

Answer

Chromosome 14

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

On this page

Practice by Chapter

Want unlimited practice?