Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology Indian Medical PG Practice Questions and MCQs

Question 771: Which gene is mutated in Waardenburg syndrome?

A. PAX2 gene
B. PAX3 gene (Correct Answer)
C. PAX6 gene
D. PAX9 gene

Explanation: ***PAX3 gene*** - Mutations in the **PAX3 gene** are the most common cause of **Waardenburg syndrome type 1 (WS1)** and **type 3 (WS3)**. - The PAX3 gene is crucial for the development of **melanocytes** and structures derived from the **neural crest**, explaining the characteristic pigmentary abnormalities and craniofacial features of the syndrome. *PAX2 gene* - Mutations in the **PAX2 gene** are primarily associated with conditions affecting **kidney and ear development**, such as **renal-coloboma syndrome**. - It plays a critical role in **renal and optic nerve development**, which are generally not the primary features of Waardenburg syndrome. *PAX6 gene* - The **PAX6 gene** is a master control gene for **eye development** and is associated with conditions like **aniridia** (absence of the iris). - Its mutations typically lead to severe ocular malformations, which are distinct from the general presentation of Waardenburg syndrome. *PAX9 gene* - **PAX9 gene** mutations are linked to **tooth agenesis** or **oligodontia**, affecting the development and eruption of teeth. - This gene is particularly involved in **odontogenesis** and craniofacial development, but not typically in the pigmentary or hearing defects seen in Waardenburg syndrome.

Question 772: Duchenne's muscular dystrophy follows which inheritance pattern?

A. X-Linked dominant
B. X-Linked recessive (Correct Answer)
C. Autosomal dominant
D. Autosomal recessive

Explanation: ***X-Linked recessive*** - **Duchenne's muscular dystrophy (DMD)** is a classic example of an **X-linked recessive** genetic disorder, primarily affecting males. - The gene responsible for producing **dystrophin** is located on the X chromosome; males have only one X chromosome, so a single defective copy leads to the disease. *X-Linked dominant* - In **X-linked dominant** disorders, only one copy of the affected gene on the X chromosome is sufficient to cause the disorder, affecting both males and females, but often with more severe manifestations in males. - Examples include **Fragile X syndrome** and **Rett syndrome**, which do not fit the clinical presentation of DMD. *Autosomal dominant* - **Autosomal dominant** disorders are caused by a mutation in a single copy of a gene on one of the **non-sex chromosomes** (autosomes). - This inheritance pattern means that an affected individual has a 50% chance of passing the disorder to each child, regardless of sex, which is not characteristic of DMD. *Autosomal recessive* - **Autosomal recessive** disorders require an individual to inherit two copies of the mutated gene (one from each parent) to develop the condition. - While other muscular dystrophies like **limb-girdle muscular dystrophy** can be autosomal recessive, DMD specifically follows an X-linked recessive pattern.

Question 773: Deficiency of which of the following micronutrients results in Menkes syndrome?

A. Magnesium
B. Copper (Correct Answer)
C. Selenium
D. Manganese

Explanation: **Copper** - **Menkes syndrome** is a genetic disorder caused by a defect in the **ATP7A gene**, leading to impaired cellular copper transport and severe **copper deficiency**. - This deficiency affects multiple organ systems, resulting in characteristic features like **kinky hair**, **neurological degeneration**, and connective tissue abnormalities. *Magnesium* - Magnesium deficiency is associated with conditions like **hypomagnesemia**, muscle weakness, and cardiac arrhythmias. - It plays crucial roles in enzyme function and nerve conduction but is not directly linked to Menkes syndrome. *Selenium* - Selenium deficiency can cause **Keshan disease** (cardiomyopathy) and **myxedematous endemic cretinism**. - While an essential trace element, its deficiency does not lead to Menkes syndrome. *Manganese* - Manganese is a cofactor for several enzymes involved in metabolism and antioxidant defense. - Deficiency is rare and typically presents with impaired growth and bone development, which are distinct from Menkes syndrome.

Question 774: Which enzyme deficiency causes Niemann-Pick disease, leading to lysosomal dysfunction?

A. Ceramidase
B. Phospholipase C
C. Beta-galactosidase
D. Sphingomyelinase (Correct Answer)

Explanation: ***Sphingomyelinase*** - Niemann-Pick disease types A and B are caused by a deficiency in the enzyme **acid sphingomyelinase**, which is responsible for the breakdown of **sphingomyelin**. - This deficiency leads to the accumulation of **sphingomyelin** within lysosomes of various tissues, particularly in the brain, spleen, liver, and lungs. *Ceramidase* - A deficiency in **ceramidase** causes Farber disease, a rare lysosomal storage disorder characterized by joint deformities, subcutaneous nodules, and hoarseness. - While both ceramidase and sphingomyelinase are involved in **sphingolipid metabolism**, their specific substrates and the resulting clinical pathologies differ. *Phospholipase C* - **Phospholipase C** plays a crucial role in signal transduction by cleaving phospholipids, but its deficiency is not directly linked to Niemann-Pick disease. - Deficiencies in phospholipase C activity are associated with various cellular dysfunctions but not lysosomal storage disorders like Niemann-Pick. *Beta-galactosidase* - A deficiency in **beta-galactosidase** causes GM1 gangliosidosis and Morquio syndrome type B, both of which are lysosomal storage disorders. - These conditions involve the accumulation of specific **glycosphingolipids** or **keratan sulfate**, rather than sphingomyelin.

Question 775: Which of the following conditions is associated with a defect in DNA repair mechanisms?

A. Xeroderma pigmentosum (Correct Answer)
B. Angelman syndrome
C. DiGeorge syndrome
D. Ichthyosis

Explanation: ***Xeroderma pigmentosum*** - It is a genetic disorder caused by defects in **DNA repair mechanisms**, specifically affecting the body's ability to repair UV-induced DNA damage [1]. - Patients are highly sensitive to **sun exposure**, leading to skin lesions, and have an increased risk of skin cancers due to the accumulation of unrepaired DNA damage [1,2]. *DiGeorge's syndrome* - Primarily characterized by **thymic hypoplasia** leading to immune deficiency and **hypoparathyroidism**, and does not directly involve DNA repair defects. - Associated with **chromosomal deletion (22q11.2)** but not a defect in DNA repair itself. *Icthyosis* - Refers to a group of skin disorders characterized by **thickened, dry skin**, which is not primarily related to defects in DNA repair mechanisms. - It can be inherited but lacks the association with **UV sensitivity** and skin cancer risk observed in xeroderma pigmentosum. *Angelman syndrome* - A neurodevelopmental disorder usually caused by a deletion of the **UBE3A gene** on chromosome 15, not related to DNA repair processes. - Characterized by **severe developmental delays and ataxia**, but does not involve defects in DNA repair mechanisms. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 322-323. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 332-333.

Question 776: What is the karyotype of a patient with androgen insensitivity syndrome?

A. 46,XY (Correct Answer)
B. 47,XXY
C. 48,XXYY
D. 46,XX

Explanation: ***46,XY*** - Patients with **androgen insensitivity syndrome (AIS)** are genetically male with a **46,XY karyotype**, meaning they have a Y chromosome and thus an SRY gene. - The syndrome arises from a **defect in androgen receptors**, leading to an inability of target tissues to respond to testosterone and other androgens, despite their presence. - In complete AIS, individuals have a **female external phenotype** despite being genetically male. *46,XX* - This karyotype represents a **genetically female individual** who would typically develop female secondary sexual characteristics. - Individuals with AIS are genetically male and, despite outwardly female characteristics in complete AIS, possess a Y chromosome. *47,XXY* - This karyotype describes **Klinefelter syndrome**, a condition where males have an extra X chromosome. - Individuals with Klinefelter syndrome typically present with hypogonadism, infertility, and often tall stature, which is distinct from AIS where the primary issue is androgen receptor function. *48,XXYY* - This karyotype represents a **sex chromosome aneuploidy** with two extra sex chromosomes. - Affected individuals are phenotypically male with features that may include tall stature, developmental delays, and hypogonadism. - It is not associated with androgen insensitivity syndrome, which specifically involves normal androgen production but impaired receptor function in 46,XY individuals.

Question 777: Which of the following statements about the genetic basis of Fragile X syndrome is true?

A. It is caused by a mutation in mitochondrial DNA.
B. It is associated with chromosomal instability.
C. It is caused by a CGG repeat expansion in the FMR1 gene. (Correct Answer)
D. It is caused by centromere abnormalities.

Explanation: ***Triple nucleotide repeat sequence*** - Fragile-X syndrome is caused by the **expansion of a CGG repeat** in the FMR1 gene on the X chromosome [1]. - This genetic alteration leads to **loss of function** of the FMRP protein, resulting in developmental delays and intellectual disabilities [1]. *Centrachrome absent* - Centrachrome is not a relevant term or feature associated with fragile-X syndrome. - The syndrome is characterized by specific **genetic mutations**, not the absence of centrachrome. *Chromosome breaking* - While fragile-X syndrome affects the X chromosome, it does **not involve breaking** of chromosomes in the conventional sense. - Instead, it is marked by **instability of the CGG repeats** [1], rather than actual chromosome fragmentation. *Mitochondrial mutation* - Fragile-X syndrome is not related to **mitochondrial DNA**, as it is a result of a mutation in the nuclear DNA. - Symptoms and inheritance patterns differ significantly from those of **mitochondrial disorders**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 177-181.

Question 778: Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?

A. Gene Knockout
B. Impaired DNA repair
C. Genomic Imprinting (Correct Answer)
D. RNA interference

Explanation: ***Genomic Imprinting*** - **Genomic imprinting** is an epigenetic phenomenon where certain genes are expressed in a **parent-of-origin-specific manner**. - In Prader-Willi syndrome, the disease results from the loss of function of specific genes on chromosome 15 (15q11-q13) inherited from the father, while Angelman syndrome results from the loss of function of a different gene (UBE3A) in the same region, but inherited from the mother. *RNA interference* - **RNA interference** is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules. - This process is not directly responsible for the parent-of-origin-specific expression patterns observed in these syndromes. *Gene Knockout* - A **gene knockout** is a genetic technique in which an organism's genes are made inoperative. - While it involves modifying gene function, it does not explain the differential expression based on parental origin. *Impaired DNA repair* - **Impaired DNA repair** refers to defects in the mechanisms that correct DNA damage. - This can lead to increased mutations and conditions like cancer, but it is not the underlying mechanism for Prader-Willi or Angelman syndromes.

Question 779: What term describes a chromosomal number that is an exact multiple of 23?

A. Euploidy (Correct Answer)
B. Aneuploidy
C. Mosaicism
D. Trisomy

Explanation: ***Euploidy*** - Euploidy refers to the condition where the **chromosomal number is an exact multiple of 23**, indicating a complete set of chromosomes. - This condition represents the normal state for organisms and includes multiples like **diploidy (2n)** and **triploidy (3n)**. *Aneuploidy* - Aneuploidy is an **abnormal chromosomal number** that is not a complete multiple of 23, leading to conditions like **trisomy** or **monosomy** [1]. - It typically results in **genetic disorders** such as Down syndrome (Trisomy 21) due to the presence of an extra chromosome [1]. *Trisomy* - Trisomy specifically refers to the presence of an **extra chromosome** in a pair, resulting in a total of 47 chromosomes instead of the normal 46 [1]. - It is a specific type of **aneuploidy**, making it not a complete multiple of 23 in the context discussed [1]. *Mosaicism* - Mosaicism describes a situation where an individual has **two or more genetically different cell lines**, leading to a mix of normal and abnormal cells [1]. - It does not inherently correspond to an **exact multiple** of chromosome sets, thus not applicable here [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169.

Question 780: Orotic aciduria is due to deficiency of:

A. Ornithine transcarbamylase
B. UMP synthase (Correct Answer)
C. Argininosuccinate lyase
D. Carbamoyl phosphate synthetase I

Explanation: ***UMP synthase*** - **Orotic aciduria** results from a deficiency in **UMP synthase**, a bifunctional enzyme with **orotate phosphoribosyltransferase** and **OMP decarboxylase** activities. - This deficiency leads to an accumulation of **orotic acid** due to the inability to convert **orotate** to **uridine monophosphate (UMP)**, affecting pyrimidine synthesis. *Ornithine transcarbamylase* - Deficiency in **ornithine transcarbamylase (OTC)** causes **hyperammonemia** and increased plasma **glutamine**, as it's involved in the urea cycle. - While it causes elevated **orotic acid**, this accumulation is due to excess **carbamoyl phosphate** shunting to pyrimidine synthesis, not a direct pyrimidine synthesis defect. *Argininosuccinate lyase* - A deficiency in **argininosuccinate lyase** leads to **argininosuccinic aciduria**, characterized by the accumulation of **argininosuccinic acid** and **hyperammonemia**. - This enzyme is also part of the **urea cycle**, and its dysfunction does not directly cause **orotic aciduria** as its primary symptom. *Carbamoyl phosphate synthetase I* - Deficiency of **carbamoyl phosphate synthetase I (CPS1)** results in severe **hyperammonemia** immediately after birth, as it's the first enzyme in the **urea cycle**. - Unlike **OTC deficiency**, CPS1 deficiency typically does not lead to **elevated orotic acid**, because the upstream precursor **carbamoyl phosphate** is not overproduced and shunted to pyrimidine synthesis.

Practice by Chapter

Single Gene Disorders

Practice Questions

Biochemical Diagnosis of Genetic Disorders

Practice Questions

Inborn Errors of Metabolism

Practice Questions

Lysosomal Storage Diseases

Practice Questions

Glycogen Storage Diseases

Practice Questions

Disorders of Lipoprotein Metabolism

Practice Questions

Disorders of Purine and Pyrimidine Metabolism

Practice Questions

Hemoglobinopathies

Practice Questions

Porphyrias

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Biochemical Markers for Disease Diagnosis

Practice Questions

Newborn Screening for Genetic Disorders

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Enzyme Replacement Therapy

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