Genetic Disorders — MCQs
Which of the following translocations is not associated with Down syndrome?
Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
Inheritance of Huntington's disease is
An affected male does not have affected children but an affected female always has affected children. Type of inheritance?
Differential expression of the same gene depending on parent of origin is referred to as
Kinky hair disease is a disorder where an affected child has peculiar white stubby hair, does not grow, brain degeneration is seen and dies by age of two years. Mrs A is hesitant about having children because her two sisters had sons who died from kinky hair disease. Her mother's brother also died of the same condition. Which of the following is the possible mode of inheritance in her family?
Number of chromosomes in Klinefelter syndrome:
A teenage girl presents with a history of amenorrhea. Local examination is shown in the image. What karyotype analysis would you consider for further evaluation?
Which one of the following is an autosomal recessive disorder?
What is the type of inheritance in MELAS?
Genetic Disorders Indian Medical PG Practice Questions and MCQs
Question 1: Which of the following translocations is not associated with Down syndrome?
- A. t(21;21)
- B. t(14;21)
- C. t(15;21)
- D. t(11;14) (Correct Answer)
Explanation: ***t (11: 14)*** - The **t(11;14) translocation** is commonly associated with **mantle cell lymphoma**, a B-cell non-Hodgkin lymphoma, and is not a cause of Down syndrome. - This translocation leads to the overexpression of the **cyclin D1 gene**, located on chromosome 11, which promotes cell growth and proliferation. *t (14; 21)* - This is a common **Robertsonian translocation** involving chromosomes 14 and 21, which results in an extra copy of chromosome 21 material [1]. - Individuals with this translocation can have **Down syndrome** because their cells end up with the equivalent of three copies of chromosome 21 [1]. *t (21; 21)* - This translocation is another type of **Robertsonian translocation** where two chromosome 21s fuse. - This specific translocation is rare and results in an extra copy of chromosome 21, leading to **Down syndrome** with a high recurrence risk in offspring. *t (15: 21)* - This is a **Robertsonian translocation** involving chromosomes 15 and 21, resulting in an extra copy of chromosome 21 material. - This translocation is a known cause of **Down syndrome** due to the dosage imbalance of genes on chromosome 21 [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 169-172.
Question 2: 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 3: Inheritance of Huntington's disease is
- A. Autosomal Dominant (Correct Answer)
- B. X-Linked Recessive
- C. Autosomal Recessive
- D. X-Linked Dominant
Explanation: ***AD*** - Huntington's chorea is inherited in an **autosomal dominant** manner, meaning only one copy of the mutated gene is sufficient to cause the disorder [1]. - The disease typically manifests in mid-adulthood, with progressively worsening movement disorders and cognitive decline [1]. *XR* - X-linked recessive disorders typically affect **males** and can be transmitted by carrier females; this is not the case for Huntington's chorea. - The inheritance pattern does not align with the typical clinical presentation of Huntington's, which does not show a gender bias. *XD* - X-linked dominant disorders often affect both sexes, but their inheritance pattern does not describe Huntington's chorea. - Symptoms and gene affected are clearly linked with **autosomal dominant** inheritance, not X-linked dominant. *AR* - Autosomal recessive conditions typically require two copies of the mutated gene, which is not applicable to Huntington's chorea. - This pattern generally leads to earlier onset conditions and significantly different clinical presentations than those observed in Huntington's. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 149-150.
Question 4: An affected male does not have affected children but an affected female always has affected children. Type of inheritance?
- A. Autosomal recessive
- B. Mitochondrial (Correct Answer)
- C. X linked recessive
- D. X linked dominant
Explanation: ***Correct Option: Mitochondrial*** - This pattern describes **mitochondrial inheritance**, where all children of an **affected mother** inherit the condition because mitochondria are exclusively inherited from the ovum (maternal inheritance). - An **affected father** cannot pass on the condition to his children, as sperm contribute only nuclear DNA and essentially no mitochondria. - This is the **only inheritance pattern** where an affected male has no affected children while an affected female has all children affected. *Incorrect Option: Autosomal recessive* - This pattern would typically show affected individuals having unaffected parents (who are carriers) and both males and females being affected in equal proportions. - It does not explain the complete absence of transmission from an affected father or universal transmission from an affected mother. - An affected individual could have unaffected children if their partner is not a carrier. *Incorrect Option: X linked recessive* - In **X-linked recessive inheritance**, affected males cannot pass the trait to their sons, but all their daughters would be carriers (not affected). - An affected mother would pass the trait to all her sons (affected) and make all her daughters carriers (not affected), which does not match the described pattern of all children being affected. *Incorrect Option: X linked dominant* - In **X-linked dominant inheritance**, an affected father passes the trait to all his daughters but none of his sons (contradicts "no affected children"). - An affected mother has a 50% chance of passing the trait to **each child**, which is inconsistent with all children of an affected female being affected.
Question 5: Differential expression of the same gene depending on parent of origin is referred to as
- A. Mosaicism
- B. Nonpenetrance
- C. Anticipation
- D. Genomic imprinting (Correct Answer)
Explanation: ***Genomic imprinting*** - This phenomenon describes the differential expression of a gene based on its **parent of origin**, meaning that the gene is expressed only from the allele inherited from a specific parent (either maternal or paternal). - This differential expression occurs without altering the underlying DNA sequence and is often mediated by **epigenetic mechanisms** such as DNA methylation. *Mosaicism* - This refers to the presence of **two or more populations of cells** with different genotypes within a single individual who has developed from a single fertilized egg. - It does not involve differential expression of the same gene based on parental origin, but rather **genetic differences arising after fertilization**. *Nonpenetrance* - **Nonpenetrance** describes a situation where an individual carries a disease-causing gene mutation but **does not express the associated phenotype** or clinical symptoms. - This concept explains variability in disease manifestation, not differential gene expression based on parental origin. *Anticipation* - **Anticipation** is a phenomenon in genetic disorders where the symptoms become **more severe** and/or appear at an **earlier age** in successive generations. - This is often seen in disorders caused by expansion of trinucleotide repeats, such as Huntington's disease, and is not related to parent-of-origin gene expression.
Question 6: Kinky hair disease is a disorder where an affected child has peculiar white stubby hair, does not grow, brain degeneration is seen and dies by age of two years. Mrs A is hesitant about having children because her two sisters had sons who died from kinky hair disease. Her mother's brother also died of the same condition. Which of the following is the possible mode of inheritance in her family?
- A. X-linked recessive (Correct Answer)
- B. Autosomal dominant
- C. X-linked dominant
- D. Autosomal recessive
Explanation: ***X-linked recessive*** - Kinky hair disease (Menkes disease) is an **X-linked recessive disorder**, meaning that males are predominantly affected, and females are carriers. - The pattern of inheritance in the family (sons of sisters, and a maternal uncle affected) is highly suggestive of **X-linked recessive inheritance**, as healthy female carriers can pass the gene to their sons. *Autosomal dominant* - In **autosomal dominant** inheritance, the disease would affect individuals in every generation, and both males and females would be affected equally. - This pattern of inheritance does not explain why only sons are dying and why sisters (who are likely carriers) are unaffected but have affected children. *X-linked dominant* - In **X-linked dominant** inheritance, affected fathers would pass the trait to all their daughters, and affected mothers would pass it to half of their children. - The disease would also be more common in females, which contradicts the described pattern of only sons being affected and dying. *Autosomal recessive* - In **autosomal recessive** inheritance, both parents must be carriers for a child to be affected, and typically, there would be a 25% chance of recurrence in each pregnancy. - This mode doesn't explain the observation of affected maternal uncles and sons from sisters, which points more directly to an X-linked pattern where females are carriers.
Question 7: Number of chromosomes in Klinefelter syndrome:
- A. 44
- B. 46
- C. 47 (Correct Answer)
- D. 45
Explanation: ***47*** - **Klinefelter syndrome** is a genetic condition in males characterized by the presence of an extra X chromosome, resulting in a **47, XXY karyotype** [1]. - This additional chromosome increases the total count from the typical 46 to **47** [1]. *44* - A count of 44 chromosomes would indicate either a severe **aneuploidy** or a **haploid** state, which is not compatible with human life in a full somatic cell. - Normal human somatic cells contain 46 chromosomes (2n). *46* - A count of 46 chromosomes represents the **normal diploid number** for human somatic cells (46, XX for females and 46, XY for males). - This count would signify a genetically typical individual, not someone with Klinefelter syndrome. *45* - A count of 45 chromosomes typically indicates a **monosomy**, such as **Turner syndrome** (45, X) in females, where one sex chromosome is missing. - This is a different chromosomal abnormality from Klinefelter syndrome, which involves an extra chromosome. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 92-93.
Question 8: A teenage girl presents with a history of amenorrhea. Local examination is shown in the image. What karyotype analysis would you consider for further evaluation?
- A. 46 XY
- B. 46 XX
- C. 45 XO (Correct Answer)
- D. 47 XXY
- E. 47 XXX
Explanation: ***45 XO*** - The image shows a **webbed neck** and **short stature** (suggested by the overall body proportions typically associated with Ullrich-Turner Syndrome), alongside primary amenorrhea, which are classic features of **Turner Syndrome**. - **Turner Syndrome** is a chromosomal disorder characterized by the absence of all or part of one X chromosome in females, resulting in a **45, XO karyotype**. *46 XY* - This karyotype indicates a **phenotypic male** with normal male chromosomal constitution. - Individuals with this karyotype would not typically present with **primary amenorrhea** as they do not have a uterus. *46 XX* - This is the **normal female karyotype**, and while a female with this karyotype could experience amenorrhea (e.g., due to Asherman's syndrome or PCOS), the physical features associated with the image (like webbed neck) are not consistent. - This option does not explain the **physical stigmata** often seen in genetic causes of primary amenorrhea, such as in Turner syndrome. *47 XXY* - This karyotype is characteristic of **Klinefelter Syndrome**, which affects males and is associated with hypogonadism and gynecomastia. - It would not be found in a female patient presenting with **amenorrhea** and the physical features shown in the image. *47 XXX* - This karyotype represents **Triple X Syndrome** (Trisomy X), which affects females and typically presents with **normal female appearance** and often normal fertility. - While some individuals may have menstrual irregularities, the **distinctive physical features** shown in the image (webbed neck, short stature) are not characteristic of Triple X syndrome, which usually lacks specific dysmorphic features.
Question 9: Which one of the following is an autosomal recessive disorder?
- A. Cystic fibrosis (Correct Answer)
- B. Huntington's disease
- C. Marfan syndrome
- D. Neurofibromatosis type 1
Explanation: ***Cystic fibrosis*** - **Cystic fibrosis** is caused by mutations in the **CFTR gene**, leading to defective **chloride channel** function. - It is an **autosomal recessive disorder**, meaning an individual must inherit two copies of the mutated gene (one from each parent) to be affected. *Huntington's disease* - **Huntington's disease** is an **autosomal dominant disorder** caused by a mutation in the HTT gene. - Only one copy of the mutated gene is sufficient to cause the disease, resulting in progressive neurodegeneration. *Marfan syndrome* - **Marfan syndrome** is an **autosomal dominant disorder** affecting connective tissue, caused by mutations in the FBN1 gene. - It results in skeletal, ocular, and cardiovascular abnormalities due to defective **fibrillin-1**. *Neurofibromatosis type 1* - **Neurofibromatosis type 1** is an **autosomal dominant disorder** caused by mutations in the NF1 gene. - It is characterized by multiple neurofibromas, café-au-lait macules, and Lisch nodules.
Question 10: What is the type of inheritance in MELAS?
- A. X-linked Recessive
- B. Autosomal Recessive
- C. Mitochondrial (Correct Answer)
- D. X-linked Dominant
Explanation: ***Mitochondrial*** - **MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes)** is caused by mutations in **mitochondrial DNA**. - **Mitochondrial inheritance** shows **maternal transmission** - the disease is passed from mothers to all of their children (both sons and daughters), but **only daughters can transmit it to the next generation** as sons do not pass on mitochondrial DNA. - This occurs because mitochondria are inherited exclusively from the egg (maternal), not from sperm. *X-linked Recessive* - **X-linked recessive disorders** primarily affect males, as they only have one X chromosome. - The disease is typically transmitted by carrier mothers to their sons, which is not characteristic of MELAS. *Autosomal Recessive* - In **autosomal recessive inheritance**, an individual must inherit two copies of the mutated gene (one from each parent) to be affected. - This pattern of inheritance does not explain the strict maternal transmission observed in MELAS. *X-linked Dominant* - **X-linked dominant disorders** can affect both males and females, but females are often more mildly affected. - All daughters of an affected father will inherit the condition, which differs from the maternal-only inheritance pattern of MELAS.
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