Genetic Disorders and Biochemical Pathology — MCQs

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?

Q657

Gene for the ryanodine receptor, mutation in which is responsible for malignant hyperthermia is located on which chromosome-

Q658

Which of the following statements is/are true:

Q659

Increasing severity of intellectual disability of male members over generations is a result of ?

Q660

Most common deficient enzyme in Congenital adrenal hyperplasia:

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

Question 651: BRCA1 gene lies on chromosome

A. 18
B. 21
C. 20
D. 17 (Correct Answer)

Explanation: ***Correct: 17*** - The **BRCA1 gene** is located on the long arm (q arm) of **chromosome 17** at position 21 (17q21). - This gene is a **tumor suppressor gene** involved in DNA repair, and mutations are strongly associated with increased risk of breast and ovarian cancers. *Incorrect: 18* - Chromosome 18 is associated with different genetic conditions, such as **Edwards syndrome** (trisomy 18), but not directly with BRCA1. - No major tumor suppressor genes like BRCA1 are primarily located on chromosome 18. *Incorrect: 21* - Chromosome 21 is known for being related to **Down syndrome** (trisomy 21). - It does not house the BRCA1 gene. *Incorrect: 20* - While chromosome 20 contains genes involved in various functions, it is **not the location of the BRCA1 gene**. - No significant link between BRCA1 and chromosome 20 has been identified.

Question 652: Which of the following is a sex-linked disorder?

A. Hemophilia (Correct Answer)
B. Neurofibromatosis
C. Klinefelter's syndrome
D. Thalassemia

Explanation: ***Hemophilia*** - Hemophilia is an **X-linked recessive disorder**, meaning the gene responsible is located on the X chromosome. - Males are predominantly affected because they have only one X chromosome, so a single copy of the mutated gene is sufficient to cause the disease. *Neurofibromatosis* - Neurofibromatosis is an **autosomal dominant disorder**, meaning a single copy of the mutated gene on a non-sex chromosome is enough to cause the condition. - It affects males and females equally and is characterized by tumors along nerves and skin changes. *Klinefelter's syndrome* - Klinefelter's syndrome is a **chromosomal disorder** resulting from an extra X chromosome in males (XXY), not a single gene mutation on a sex chromosome. - While it involves sex chromosomes, it's categorized as a **sex chromosome aneuploidy** rather than a sex-linked disorder in the traditional genetic sense. *Thalassemia* - Thalassemia is an **autosomal recessive disorder**, meaning it requires two copies of the mutated gene (one from each parent) on non-sex chromosomes to manifest. - It affects the production of hemoglobin and impacts males and females equally.

Question 653: Maroteaux-Lamy syndrome is characterized by deficiency of

A. Arylsulfatase B (Correct Answer)
B. Beta Glucuronidase
C. Iduronate sulfatase
D. Beta Galactosidase

Explanation: ***Arylsulfatase B*** - **Maroteaux-Lamy syndrome (MPS VI)** is caused by a deficiency of the enzyme **arylsulfatase B (ARSB)**, also known as N-acetylgalactosamine-4-sulfatase. - This enzyme deficiency leads to the accumulation of **dermatan sulfate** within lysosomes. *Beta Glucuronidase* - Deficiency of **beta-glucuronidase** is associated with **Sly syndrome (MPS VII)**, which has a distinct clinical presentation. - This enzyme is responsible for the degradation of **dermatan sulfate** and **heparan sulfate**. *Iduronate sulfatase* - Deficiency of **iduronate sulfatase** causes **Hunter syndrome (MPS II)**, leading to accumulation of heparan sulfate and dermatan sulfate. - Hunter syndrome has X-linked inheritance, distinguishing it from Maroteaux-Lamy syndrome. *Beta Galactosidase* - Deficiency of **beta-galactosidase** is responsible for **GM1 gangliosidosis** and **Morquio syndrome type B (MPS IVB)**. - These conditions have different clinical features and biochemical abnormalities compared to Maroteaux-Lamy syndrome.

Question 654: In X-linked recessive inheritance, the risk of a female carrier having an affected child is

A. 75
B. 100
C. 50
D. 25 (Correct Answer)

Explanation: ***25*** - A female carrier of an **X-linked recessive disorder** has two X chromosomes, one with the normal allele and one with the mutated allele. - For each pregnancy, there is a **25% chance** that the child will be an **affected male (XY)**, inheriting the mutated X chromosome from the mother and the Y chromosome from the father. *75* - This percentage is incorrect; it would represent the probability of an unaffected child in the case of a **dominant autosomal disorder** with one affected and one unaffected parent. - In X-linked inheritance, the risks are specifically broken down based on the child's sex. *100* - This percentage would apply if both parents were homozygous for a **recessive condition** or if a dominant condition had 100% penetrance and one parent was homozygous dominant. - X-linked inheritance from a carrier mother does not result in 100% affected offspring, as there are other possible genetic outcomes. *50* - This percentage represents the chance of a child inheriting any single allele from a heterozygous parent. - While it's true there's a 50% chance for a male child to be affected, and a 50% chance for a female child to be a carrier, the overall risk of **any affected child (male or female)** from a carrier mother is 25%.

Question 655: Inheritance of Gardner syndrome is

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

Explanation: ***Autosomal dominant*** - Gardner syndrome is a variant of **familial adenomatous polyposis (FAP)**, inherited in an **autosomal dominant** pattern. - It is caused by a germline mutation in the **APC gene** (adenomatous polyposis coli) on chromosome 5q21-q22. *Autosomal recessive* - Autosomal recessive disorders require **two copies of the mutated gene** (one from each parent) to manifest, which is not the inheritance pattern for Gardner syndrome. - Examples include **cystic fibrosis** or **sickle cell anemia**, where both parents are typically carriers. *X-linked recessive* - **X-linked recessive** disorders primarily affect males, as the mutated gene is located on the X chromosome, and females are usually carriers. - Gardner syndrome affects both sexes equally and is not linked to the X chromosome. *X-linked dominant* - In **X-linked dominant** inheritance, a single copy of the mutated gene on the X chromosome can cause the disorder, affecting both males and females, though often more severely in males. - However, Gardner syndrome is not X-linked, but rather an autosomal condition.

Question 656: 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 657: Gene for the ryanodine receptor, mutation in which is responsible for malignant hyperthermia is located on which chromosome-

A. Chromosome 19 (Correct Answer)
B. Chromosome 16
C. Chromosome 17
D. Chromosome 18

Explanation: ***Chromosome 19*** - The gene encoding the **ryanodine receptor type 1 (RYR1)**, crucial for regulating calcium release from the sarcoplasmic reticulum, is located on **chromosome 19q13.1**. - Mutations in the **RYR1 gene** are the primary cause of **malignant hyperthermia susceptibility (MHS)**, an inherited disorder triggering a hypermetabolic crisis during exposure to certain anesthetics. *Chromosome 16* - Chromosome 16 is associated with various genetic conditions, such as **Crohn's disease**, **autosomal dominant polycystic kidney disease**, and certain forms of **epilepsy**. - However, it does not harbor the **RYR1 gene** or play a direct role in the etiology of malignant hyperthermia. *Chromosome 17* - Chromosome 17 contains genes linked to diseases like **Neurofibromatosis type 1**, **hereditary breast and ovarian cancer (BRCA1 gene)**, and **Smith-Magenis syndrome**. - It is not implicated in the genetic basis of **malignant hyperthermia**. *Chromosome 18* - Relevant disorders associated with chromosome 18 include **Edwards syndrome (Trisomy 18)** and **deletion 18q syndrome**. - This chromosome is not known to carry the **RYR1 gene** or contribute to the development of malignant hyperthermia.

Question 658: Which of the following statements is/are true:

A. In a mosaic, genetically different cell types arise from a single zygote.
B. All of the options (Correct Answer)
C. In chimeras, they arise from more than one zygote.
D. Turner's syndrome survivors are often mosaics with a substantial fraction of normal cells.

Explanation: ***Correct: All of the options*** - All three statements accurately describe key concepts in genetic variation: mosaicism, chimerism, and clinical genetics of Turner syndrome. - Each statement is factually correct and represents important knowledge for medical examinations. *Correct Statement A: In a mosaic, genetically different cell types arise from a single zygote.* - **Mosaicism** occurs when a single fertilized egg develops into an individual with two or more genetically distinct cell lines - This results from **post-zygotic mutations** or chromosomal abnormalities during early embryonic cell divisions - Classic examples include McCune-Albright syndrome and some cases of chromosomal aneuploidies *Correct Statement C: Turner's syndrome survivors are often mosaics with a substantial fraction of normal cells.* - Many individuals with **Turner syndrome (45,X)** who survive have **mosaic karyotypes** such as 45,X/46,XX - The presence of a **normal 46,XX cell line** is associated with milder phenotypes and better survival - Mosaicism explains the wide phenotypic variability seen in Turner syndrome patients - However, non-mosaic 45,X individuals can also survive, though they may have more severe manifestations *Correct Statement D: In chimeras, they arise from more than one zygote.* - **Chimerism** occurs when cells from two or more different zygotes combine into a single individual - This can result from **fusion of dizygotic twin embryos** or maternal-fetal cell exchange - Unlike mosaics (one zygote → multiple cell lines), chimeras have cells from multiple fertilization events - Blood chimeras can occur after bone marrow transplantation

Question 659: Increasing severity of intellectual disability of male members over generations is a result of ?

A. Y linked disorder
B. Frameshift mutation
C. Trinucleotide repeat mutation (Correct Answer)
D. Mitochondrial DNA mutation

Explanation: ***Trinucleotide repeat mutation*** - This phenomenon, known as **anticipation**, is characteristic of disorders caused by trinucleotide repeat expansions like **Fragile X syndrome**, where the number of repeats increases in successive generations, leading to earlier onset and more severe symptoms. - The expansion of these repeats often occurs during **meiosis**, particularly **oogenesis** for Fragile X, contributing to the increasing severity observed in offspring. *Y linked disorder* - Y-linked disorders affect only males and are passed from father to son, but they do not typically show increasing severity over generations or the phenomenon of anticipation. - Their inheritance pattern is straightforward and generally consistent across generations, without progressive phenotypic changes. *Frameshift mutation* - A **frameshift mutation** involves the insertion or deletion of nucleotides that are not multiples of three, leading to a shift in the reading frame and an altered protein sequence. - While they can cause severe genetic disorders, **frameshift mutations** do not typically explain the observed increase in severity across generations (anticipation). *Mitochondrial DNA mutation* - Mitochondria are inherited exclusively from the mother, and mutations in **mitochondrial DNA** can cause a range of disorders affecting energy production. - While these disorders can vary in severity due to **heteroplasmy**, they do not typically show a pattern of increasing severity in successive generations due to an expanding repeat sequence.

Question 660: Most common deficient enzyme in Congenital adrenal hyperplasia:

A. 21-hydroxylase deficiency (Correct Answer)
B. 18-hydroxylase deficiency
C. 3-beta-hydroxysteroid dehydrogenase deficiency
D. 17-alpha hydroxylase deficiency

Explanation: ***21-hydroxylase deficiency*** - This is by far the **most common cause** of congenital adrenal hyperplasia (CAH), accounting for about 90-95% of all cases. - Deficiency in 21-hydroxylase leads to impaired synthesis of **cortisol** and **aldosterone**, and an accumulation of androgen precursors. *18-hydroxylase deficiency* - This enzyme is crucial for the final step in **aldosterone synthesis**, specifically converting 18-hydroxycorticosterone to aldosterone. - Its deficiency would primarily impact **aldosterone production**, leading to salt wasting, but it is a very rare cause of CAH and does not affect cortisol synthesis directly. *3-beta-hydroxysteroid dehydrogenase deficiency* - This is a less common form of CAH that affects the synthesis of **glucocorticoids, mineralocorticoids, and androgens**. - It results in the accumulation of **dehydroepiandrosterone (DHEA)**, leading to varying degrees of virilization in females and undervirilization in males. *17-alpha hydroxylase deficiency* - This rare form of CAH impairs the production of **cortisol** and **androgens**, but it spares **aldosterone synthesis**. - Patients typically present with **hypertension** and **hypokalemia** due to excess mineralocorticoid activity, along with sexual developmental abnormalities.

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