Genetic Disorders and Biochemical Pathology Practice Questions

Q: Duchenne's muscular dystrophy follows which inheritance pattern?

X-Linked recessive. ***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.

Q: Which gene is mutated in Waardenburg syndrome?

PAX3 gene. ***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.

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

Copper. **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.

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

46,XY. ***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.

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

It is caused by a CGG repeat expansion in the FMR1 gene.. ***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.

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

Genomic Imprinting. ***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.

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

Euploidy. ***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.

Q: Orotic aciduria is due to deficiency of:

UMP synthase. ***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.

Q: Which of the following statements about 21-Hydroxylase deficiency is false?

It leads to male pseudohermaphroditism.. ***It leads to male pseudohermaphroditism.*** - **21-Hydroxylase deficiency** does not lead to male pseudohermaphroditism; instead, it causes **virilization in females** (female pseudohermaphroditism) due to increased androgen production. - Males with 21-hydroxylase deficiency typically present with **salt-wasting crises** or **premature pubarche**, but their internal and external genitalia are normal. *It is the most common cause of congenital adrenal hyperplasia.* - This statement is **true**. **21-hydroxylase deficiency** accounts for approximately 90-95% of all cases of congenital adrenal hyperplasia (CAH) [1]. - Its prevalence and significant role in cortisol and aldosterone synthesis pathways make it the predominant form of the disorder [1]. *It is inherited in an autosomal recessive manner.* - This statement is **true**. 21-hydroxylase deficiency is caused by mutations in the **CYP21A2 gene**, which is inherited in an **autosomal recessive pattern**. - Both parents must be carriers for a child to be affected, with each child having a 25% chance of inheriting the disorder. *It leads to female pseudohermaphroditism.* - This statement is **true**. In affected females, the deficiency of 21-hydroxylase shunts steroid precursors towards the **androgen pathway**, leading to excess adrenal androgens. - This excess androgen exposure *in utero* causes **virilization** of external genitalia, resulting in varying degrees of **ambiguous genitalia** (female pseudohermaphroditism).

Q: Pedigree analysis chart is a tool used for which of the following purposes?

Used to see genetic transmission. ***Used to see genetic transmission*** - A **pedigree chart** is a visual representation of biological relationships and genetic traits across multiple generations of a family. - It helps determine the **inheritance pattern** of a particular trait or disease within a family, such as autosomal dominant, recessive, or X-linked. *Used for growth monitoring* - **Growth monitoring** typically involves plotting an individual's weight, height, and head circumference on growth charts over time. - While family data might be considered, a pedigree chart is not the primary tool for directly monitoring an individual's physical growth. *To assess side effects during chemotherapy* - Assessing **side effects during chemotherapy** involves clinical evaluations, laboratory tests (e.g., blood counts, organ function tests), and patient self-reporting. - A pedigree chart provides information about family history and genetic predisposition, not direct monitoring of treatment side effects. *To assess developmental delay in infants* - **Developmental delay assessment** involves observing a child's milestone achievement in areas like motor skills, language, and cognition, often using standardized screening tools. - While some developmental delays can have genetic causes that might be highlighted in a pedigree, the chart itself does not directly assess developmental progress.

Question 1

Duchenne's muscular dystrophy follows which inheritance pattern?

Accepted Answer

X-Linked recessive

Answer

X-Linked dominant

Answer

Autosomal dominant

Answer

Autosomal recessive

Question 2

Which gene is mutated in Waardenburg syndrome?

Accepted Answer

PAX3 gene

Answer

PAX2 gene

Answer

PAX6 gene

Answer

PAX9 gene

Question 3

Deficiency of which of the following micronutrients results in Menkes syndrome?

Accepted Answer

Copper

Answer

Magnesium

Answer

Selenium

Answer

Manganese

Question 4

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

Accepted Answer

46,XY

Answer

47,XXY

Answer

48,XXYY

Answer

46,XX

Question 5

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

Accepted Answer

It is caused by a CGG repeat expansion in the FMR1 gene.

Answer

It is caused by a mutation in mitochondrial DNA.

Answer

It is associated with chromosomal instability.

Answer

It is caused by centromere abnormalities.

Question 6

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

Accepted Answer

Genomic Imprinting

Answer

Gene Knockout

Answer

Impaired DNA repair

Answer

RNA interference

Question 7

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

Accepted Answer

Euploidy

Answer

Aneuploidy

Answer

Mosaicism

Answer

Trisomy

Question 8

Orotic aciduria is due to deficiency of:

Accepted Answer

UMP synthase

Answer

Ornithine transcarbamylase

Answer

Argininosuccinate lyase

Answer

Carbamoyl phosphate synthetase I

Question 9

Which of the following statements about 21-Hydroxylase deficiency is false?

Accepted Answer

It leads to male pseudohermaphroditism.

Answer

It leads to female pseudohermaphroditism.

Answer

It is the most common cause of congenital adrenal hyperplasia.

Answer

It is inherited in an autosomal recessive manner.

Question 10

Pedigree analysis chart is a tool used for which of the following purposes?

Accepted Answer

Used to see genetic transmission

Answer

Used for growth monitoring

Answer

To assess side effects during chemotherapy

Answer

To assess developmental delay in infants

Genetic Disorders and Biochemical Pathology — MCQs

Genetic Disorders and Biochemical Pathology — MCQs

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