Question 1

In contrast to mutations associated with Duchenne muscular dystrophy, what is a feature of the mutations associated with Becker muscular dystrophy?

Accepted Answer

Becker muscular dystrophy mutations often result in a partially functional or truncated dystrophin protein, unlike Duchenne muscular dystrophy mutations, which typically prevent the production of any functional dystrophin.

Question 2

a1-antitrypsin deficiency leads to excess activity of which enzyme?

Accepted Answer

A1-antitrypsin deficiency results in decreased inhibition of elastase, an enzyme that breaks down elastin in the lungs, leading to excess activity of elastase.

Question 3

Which of the following is the most common CFTR mutation in white populations?

Accepted Answer

The most common CFTR mutation in white populations is the deletion of phenylalanine at position 508, often denoted as ΔF508 or F508del. This mutation affects the CFTR protein's folding and trafficking, leading to cystic fibrosis.

Question 4

Mutations in the dystrophin gene cause which phenotype?

Accepted Answer

Mutations in the dystrophin gene can lead to both Duchenne muscular dystrophy and Becker muscular dystrophy, depending on the nature and location of the mutation within the gene.

Question 5

What observation has facilitated genetic testing for Tay-Sachs disease in the Ashkenazi Jewish population?

Accepted Answer

Three specific mutations in the HEXA gene account for the majority of Tay-Sachs disease alleles in the Ashkenazi Jewish population, making genetic testing more straightforward.

Question 6

What inheritance pattern is most common for metabolic disorders?

Accepted Answer

Most metabolic disorders are inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disorder.

Question 7

How can a single gene defect lead to multiple enzyme deficiencies?

Accepted Answer

A single gene defect can lead to multiple enzyme deficiencies through various mechanisms, such as shared cofactors, similar processing pathways, common transport mechanisms, or defects in the organelle where the enzymes operate. Each of these scenarios can result in the malfunctioning of multiple enzymes, even if the primary defect is in a single gene.

Question 8

What environmental exposure greatly influences the life expectancy of individuals with the ZZ genotype for a1-antitrypsin deficiency?

Accepted Answer

Cigarette smoking greatly influences the life expectancy of individuals with the ZZ genotype for alpha-1 antitrypsin deficiency by exacerbating lung damage, leading to earlier onset and more severe forms of lung disease such as emphysema.

Question 9

Variation in which familial hypercholesterolemia-causing gene has also been associated with protection from coronary artery disease and high cholesterol levels in general populations?

Accepted Answer

Variations in the PCSK9 gene have been associated with both the cause of familial hypercholesterolemia and protection from coronary artery disease and high cholesterol levels in the general population. Certain mutations in PCSK9 can lead to lower levels of LDL cholesterol, thereby reducing the risk of coronary artery disease.

Question 10

The finding that fibroblasts from a patient with X-linked Hurler syndrome could correct the defect in fibroblasts from a patient with autosomal recessive Hurler syndrome (and vice versa) demonstrated what about the two disorders?

Accepted Answer

The finding indicates that different proteins were deficient in the two disorders, as the correction of defects between fibroblasts from patients with X-linked and autosomal recessive Hurler syndrome suggests that the deficiencies complement each other, implying different underlying protein deficiencies.

Question 11

Which of the following phenotypes is found in people with mutations in cystic fibrosis transmembrane conductance regulator (CFTR)?

Accepted Answer

Mutations in the CFTR gene can lead to a variety of phenotypes due to its role in chloride ion transport across epithelial membranes. These phenotypes include cystic fibrosis, congenital bilateral absence of the vas deferens, idiopathic chronic pancreatitis, and meconium ileus, among others.

Question 12

Which of the following properties allows enzyme replacement therapy to work for some lysosomal storage disorders?

Accepted Answer

Cells can take up enzymes from the extracellular fluid through mechanisms such as receptor-mediated endocytosis, allowing the externally supplied enzyme to enter cells and compensate for the deficient or inactive enzyme that causes the lysosomal storage disorder. This process is fundamental to the effectiveness of enzyme replacement therapy.

Question 13

The genes associated with familial hypercholesterolemia all have an effect on which protein?

Accepted Answer

Familial hypercholesterolemia is primarily associated with mutations in the gene that encodes for the low-density lipoprotein (LDL) receptor. These mutations impair the body's ability to remove LDL cholesterol from the blood, leading to high levels of LDL cholesterol and an increased risk of heart disease.

Question 14

Which of the following is the major cause of chronic pulmonary infection in individuals with cystic fibrosis?

Accepted Answer

Pseudomonas aeruginosa is the major cause of chronic pulmonary infections in individuals with cystic fibrosis, often leading to significant morbidity and mortality in this population.

Question 15

Which patients with mutations in phenylalanine hydroxylase are most likely to respond to BH₄ supplementation?

Accepted Answer

Patients with residual PAH activity are most likely to respond to BH₄ (tetrahydrobiopterin) supplementation because BH₄ is a cofactor for the enzyme phenylalanine hydroxylase. Those with some remaining activity of this enzyme can potentially increase its function with the addition of BH₄, improving the metabolism of phenylalanine.

Question 16

What phenomenon has a large effect on the phenotype of female carriers of dystrophin mutations?

Accepted Answer

X-inactivation significantly affects the phenotype of female carriers of dystrophin mutations because it leads to a mosaic expression of the normal and mutated dystrophin gene across different cells. This can result in a wide range of clinical manifestations among carriers.

Question 17

Where are GM2 ganglioside and mucopolysaccharides digested?

Accepted Answer

GM2 ganglioside and mucopolysaccharides are digested in the lysosome, where enzymes break down various macromolecules.

Question 18

If an infant is found to have hyperphenylalaninemia based on a newborn screen, but this defect doesn't respond to a low phenylalanine diet, what type of molecular defect would be suspected?

Accepted Answer

A defect in tetrahydrobiopterin (BH4) metabolism would be suspected if hyperphenylalaninemia does not respond to a low phenylalanine diet. BH4 is a cofactor for phenylalanine hydroxylase, and its deficiency can lead to hyperphenylalaninemia that is not ameliorated by dietary phenylalanine restriction.

Question 19

Why can vitamins be used to treat some enzymatic defects?

Accepted Answer

Vitamins can treat some enzymatic defects because they can increase the activity of the defective enzyme, often serve as enzyme cofactors, and can sometimes stabilize the defective enzyme, making them versatile in addressing various enzymatic issues.

Question 20

Genetic defects that impair the activity of methionine synthase are mimicked by a dietary deficiency of which vitamin?

Accepted Answer

Vitamin B12 is crucial for the function of methionine synthase, an enzyme involved in the metabolism of homocysteine to methionine. A deficiency in Vitamin B12 can mimic the genetic defects that impair the activity of this enzyme.

Quiz 12: The Molecular, Biochemical, and Cellular Basis of Genetic Disease