Genetics and Disease Practice Questions

Q: Which of the following statements about alpha-1 antitrypsin deficiency is true?

May cause cholestatic jaundice. ***All of the above*** - All listed statements accurately describe aspects of **alpha-1 antitrypsin deficiency** [1], including its nature, genetic inheritance, and potential consequences. - This condition allows **proteolytic enzymes** to damage the lungs and liver [1], among other organs, confirming all options as true. *Deficiency of protease inhibitor* - While alpha-1 antitrypsin is a **protease inhibitor** [1], the wording can be confusing as it implies a more general condition rather than specifying the genetic aspect of **alpha-1 antitrypsin deficiency**. - This oes not encompass the full clinical implications of the deficiency, making it insufficient alone to describe the condition. *Autosomal recessive* - The inheritance pattern of alpha-1 antitrypsin deficiency is actually **autosomal co-dominant**, not strictly recessive. - This means that individuals can express both normal and abnormal alleles, which this option fails to capture accurately. *May cause cholestatic jaundice* - Though **cholestatic jaundice** can occur due to liver involvement in severe cases, it is not a defining feature of the deficiency and may be considered as a rare complication. - More commonly, the condition leads to **emphysema** [1][2] and liver cirrhosis, highlighting the insufficiency of this statement on its own.

Q: Which of the following is a single gene autosomal recessive disease?

Wilson's disease. ***Wilson's disease*** - This is an **autosomal recessive disorder** [1] characterized by excessive **copper accumulation** in the liver, brain, and other organs due to a mutation in the ATP7B gene. - Manifestations include **hepatic dysfunction**, neurological symptoms, and characteristic **Kayser-Fleischer rings** in the eyes [1]. *Tuberous sclerosis* - This is an **autosomal dominant disorder** caused by mutations in the TSC1 or TSC2 genes, leading to the formation of benign tumors in multiple organs. - Clinical features include **epilepsy**, intellectual disability, facial angiofibromas, and renal angiomyolipomas. *Huntington's disease* - This is an **autosomal dominant neurodegenerative disorder** caused by a CAG trinucleotide repeat expansion in the HTT gene. - It presents with **progressive chorea**, psychiatric symptoms, and cognitive decline, typically in mid-adulthood. *Schizophrenia* - This is a **complex psychiatric disorder** with a multifactorial etiology, involving a combination of genetic predisposition and environmental factors. - It is not a single gene disorder but rather involves many genes contributing to risk, indicating a **polygenic inheritance pattern**.

Q: Mutation in the NPHS1 gene causes which of the following disease?

Congenital Finnish type nephrotic syndrome. ***Congenital Finnish type nephrotic syndrome*** - This syndrome is caused by mutations in the **NPHS1 gene**, encoding **nephrin**, a key component of the **slit diaphragm** in glomerular podocytes. - The dysfunctional nephrin leads to severe **proteinuria** and nephrotic syndrome from birth. *Alport syndrome* - This syndrome is caused by mutations in genes encoding **Type IV collagen**, primarily **COL4A5 (X-linked)**, which is crucial for basement membrane integrity [3]. - Characterized by **hematuria**, progressive renal failure, **sensorineural hearing loss**, and ocular abnormalities. *Focal segmental glomerulonephritis* - While some forms can be genetic, **NPHS1 mutations** are not typically the primary cause of genetic [1]. - This condition involves scarring of specific parts of some glomeruli and has various primary and secondary causes [2]. *Nail patella syndrome* - This syndrome is caused by mutations in the **LMX1B gene**, which plays a role in early limb and kidney development. - It is characterized by **nail dysplasia**, absent or hypoplastic patellae, elbow abnormalities, and iliac horns, sometimes with renal involvement.

Q: Which one of the following is an autosomal dominant disorder?

Hereditary spherocytosis. ***Hereditary spherocytosis*** - It is characterized by **autosomal dominant inheritance** [1], leading to the destruction of red blood cells. - Mutations in proteins that maintain the **red blood cell membrane** integrity result in spherocyte formation [1]. *Cystic fibrosis* - This condition follows a **autosomal recessive inheritance pattern**, requiring two copies of the mutated gene for disease manifestation. - It is caused by mutations in the **CFTR gene**, affecting chloride transport and leading to thick secretions. *G-6PD deficiency* - This disorder is inherited in an **X-linked recessive manner** [2], primarily affecting males and transmitted through carrier females. - Characterized by **hemolytic anemia** triggered by certain medications or infections, it does not follow dominant inheritance [2]. *Sickle cell anemia* - Sickle cell anemia is also an **autosomal recessive disorder** [3], meaning affected individuals must inherit two copies of the sickle cell gene. - It results in a mutation in the **HBB gene**, leading to the production of abnormal hemoglobin (HbS) [3].

Q: What specific hand abnormalities are associated with Marfan syndrome?

Arachnodactyly. ***Arachnodactyly*** - This term refers to **long, slender fingers and toes**, resembling a spider's appendages, which is a classic musculoskeletal manifestation of **Marfan syndrome**. - It results from the generalized connective tissue disorder affecting the deposition of **fibrillin-1**, leading to excessive bone growth. *Syndactyly* - This condition involves the **fusion of adjacent digits**, either soft tissue or bone, rather than unusually long fingers. - It is typically a congenital anomaly not specifically associated with Marfan syndrome. *Clinodactyly* - This describes the **curving or deviation of a digit**, usually the fifth finger, due to an abnormally shaped bone [1]. - While a digital anomaly, it is not a hallmark feature of Marfan syndrome, which is characterized by digit length. *Brachydactyly* - This condition is characterized by **unusually short fingers and toes**, which is the opposite of the digital characteristic seen in Marfan syndrome. - It can be a feature of various genetic disorders but not Marfan syndrome.

Q: Which of the following laboratory findings is the MOST characteristic of Wilson's disease?

Increased urinary copper excretion. ***Low ceruloplasmin and high urinary copper*** - In Wilson's disease, there is decreased **ceruloplasmin** due to impaired copper metabolism, leading to low levels in the serum [1]. - The condition results in **increased urinary copper excretion**, which is a hallmark feature and confirms the diagnosis [2]. *Low urinary copper* - Wilson's disease presents with **high urinary copper** levels due to excessive copper being expelled by the kidneys. - **Low urinary copper** would suggest a different condition, such as **Chronic liver disease** or **renal tubular disorders**. *High ceruloplasmin* - Patients with Wilson's disease have **low ceruloplasmin levels** rather than high, indicating ineffective copper transport [1]. - **High ceruloplasmin** levels are typically associated with conditions like **inflammation** or **pregnancy** rather than Wilson's disease. *Low serum copper* - In Wilson's disease, serum copper levels are typically **normal or elevated**, not low. - The primary defect is in the transport of copper, resulting in accumulation in tissues, not a deficiency in serum levels [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Liver and Gallbladder, pp. 855-856. [2] 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. 132-133.

Q: Which of the following is NOT an X-linked disease?

Cystic Fibrosis. ***DE*** - This oes not correspond to recognized **X-linked diseases**, making it the correct choice of exception. - X-linked diseases primarily include **Duchenne muscular dystrophy** [1] and **hemophilia**, which are not found in this option. *AB* - This an represent **conditions like hemophilia**, which are clearly X-linked. - Many X-linked diseases affect males more severely due to the single X chromosome. *BC* - Similar to AB, this could allude to X-linked conditions, such as **hemophilia A or B**. - X-linked inheritance patterns result in a higher prevalence in males compared to females. *CA* - May also relate to **X-linked disorders**, including **color blindness** or **Duchenne muscular dystrophy** [1]. - These diseases follow a characteristic pattern of inheritance tied to the X chromosome [1].

Q: Genetic anticipation is characteristic of:

Myotonic dystrophy. ### Myotonic dystrophy - **Genetic anticipation** is a hallmark of myotonic dystrophy, where the disease worsens and appears earlier in successive generations due to expansion of **CTG trinucleotide repeats**. - Symptoms include **myotonia** (delayed muscle relaxation), muscle wasting, cataracts, and cardiac conduction defects. ### Duchenne muscular dystrophy - This is an **X-linked recessive** disorder caused by mutations in the **dystrophin gene**, leading to progressive muscle degeneration [1], [2]. - It does not demonstrate genetic anticipation; the severity and age of onset are generally consistent within affected families. ### Emery-Dreifuss muscular dystrophy - Characterized by a classic triad of **humero-peroneal muscle weakness**, **contractures** (especially of elbows, ankles, and neck), and **cardiac conduction abnormalities**. - It is typically inherited in an X-linked, autosomal dominant, or autosomal recessive manner, but does not involve genetic anticipation. ### Becker muscular dystrophy - A milder form of muscular dystrophy than Duchenne, also caused by mutations in the **dystrophin gene**, but results in a partially functional protein. - While it is a progressive muscle weakness disorder, it does not exhibit the phenomenon of genetic anticipation.

Q: A middle-aged woman with a history of backache who underwent a Schober test and tested positive, and who also has hyperpigmented nose and ears, is most likely diagnosed with:

Ochronosis. ***Ochronosis*** - **Hyperpigmentation of the nose and ears** (due to homogentisic acid accumulation) along with **backache** and a positive **Schober test** (indicating spinal inflexibility from ochronotic arthropathy) are classic features of ochronosis. - This inherited disorder results from a deficiency of **homogentisic acid oxidase**, leading to the accumulation of homogentisic acid. *Ankylosing spondylitis* - While **backache** and a positive **Schober test** (indicating axial skeleton involvement) are characteristic of ankylosing spondylitis, it does not typically present with **hyperpigmented nose and ears**. - **HLA-B27 positivity** and inflammatory back pain improving with activity are key differentiating features not mentioned. *Degenerative disc disease* - This condition is characterized by **chronic backache** due to age-related changes in the intervertebral discs but does not cause **hyperpigmentation of the nose and ears**. - A **positive Schober test** is less specific for degenerative disc disease and is more indicative of widespread spinal stiffness. *Fluorosis* - While severe fluorosis can lead to **skeletal changes** and pain mimicking arthritis, it is primarily associated with **dental mottling** and does not cause characteristic hyperpigmentation of the nose and ears. - มัน usually results from excessive fluoride intake, often from contaminated drinking water.

Q: Which disorder is associated with NARP syndrome, characterized by neuropathy, ataxia, and retinitis pigmentosa?

Mitochondrial function disorder. ***Mitochondrial function disorder*** - NARP syndrome (Neurogenic weakness, Ataxia, Retinitis Pigmentosa) is caused by a specific point mutation in the **MT-ATP6 gene**, which encodes a subunit of the mitochondrial ATP synthase [1]. - This mutation leads to impaired mitochondrial energy production, affecting tissues with high energy demands, such as the **nervous system** and retina [1]. *Glycogen storage disorder* - These disorders involve defects in enzymes responsible for **glycogen synthesis or degradation**, leading to abnormal glycogen accumulation in tissues [1]. - While they can cause muscle weakness and neurological symptoms, the specific constellation of **neuropathy, ataxia, and retinitis pigmentosa** is not characteristic of glycogenoses. *Lysosomal storage disorder* - These conditions result from deficiencies in lysosomal enzymes, causing the accumulation of **undigested macromolecules** within lysosomes. - Symptoms vary widely but typically involve progressive neurological degeneration, organomegaly, and skeletal abnormalities, without the classic NARP presentation. *Lipid storage disorder* - These disorders are characterized by the accumulation of **specific lipids** due to enzyme deficiencies involved in lipid metabolism. - Examples include Gaucher disease and Niemann-Pick disease, which involve different clinical manifestations such as hepatosplenomegaly, bone crises, and various neurological issues, distinct from NARP syndrome.

Question 1

Which of the following statements about alpha-1 antitrypsin deficiency is true?

Accepted Answer

May cause cholestatic jaundice

Question 2

Which of the following is a single gene autosomal recessive disease?

Accepted Answer

Wilson's disease

Answer

Tuberous sclerosis

Answer

Huntington's disease

Answer

Schizophrenia

Question 3

Mutation in the NPHS1 gene causes which of the following disease?

Accepted Answer

Congenital Finnish type nephrotic syndrome

Answer

Alport syndrome

Answer

Focal segmental glomerulonephritis

Answer

nail patella syndrome

Question 4

Which one of the following is an autosomal dominant disorder?

Accepted Answer

Hereditary spherocytosis

Answer

Cystic fibrosis

Answer

Sickle cell anemia

Answer

G-6PD deficiency

Question 5

What specific hand abnormalities are associated with Marfan syndrome?

Accepted Answer

Arachnodactyly

Answer

Brachydactyly

Answer

Clinodactyly

Answer

Syndactyly

Question 6

Which of the following laboratory findings is the MOST characteristic of Wilson's disease?

Accepted Answer

Increased urinary copper excretion

Answer

Elevated serum copper

Answer

Low serum copper

Answer

Low ceruloplasmin

Question 7

Which of the following is NOT an X-linked disease?

Accepted Answer

Cystic Fibrosis

Answer

Hemophilia A

Answer

Duchenne Muscular Dystrophy

Answer

Color Blindness

Question 8

Genetic anticipation is characteristic of:

Accepted Answer

Myotonic dystrophy

Answer

Duchenne muscular dystrophy

Answer

Emery-Dreifuss muscular dystrophy

Answer

Beckers muscular dystrophy

Question 9

A middle-aged woman with a history of backache who underwent a Schober test and tested positive, and who also has hyperpigmented nose and ears, is most likely diagnosed with:

Accepted Answer

Ochronosis

Answer

Ankylosing spondylitis

Answer

Degenerative disc disease

Answer

Fluorosis

Question 10

Which disorder is associated with NARP syndrome, characterized by neuropathy, ataxia, and retinitis pigmentosa?

Accepted Answer

Mitochondrial function disorder

Answer

Glycogen storage disorder

Answer

Lysosomal storage disorder

Answer

Lipid storage disorder

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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