1. A 7-year-old boy presents with recurrent bacterial and fungal infections. He has a history of abscess formation in multiple organs. His mother is asymptomatic, but her brother had similar infections and died as a child. Genetic analysis reveals a mutation in the gene encoding NADPH oxidase. What is the most likely mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: E) X-linked recessive
Explanation:
This condition, chronic granulomatous disease, is commonly caused by a mutation in the gene encoding NADPH oxidase, located on the X chromosome. The inheritance is X-linked recessive because:
1. The boy is affected, while his mother is asymptomatic, suggesting she is a carrier.
2. The maternal uncle’s history indicates the gene mutation is passed through female carriers to males.
3. Males express the disorder because they only have one X chromosome, making them hemizygous for the defective gene.
2. A 25-year-old man presents with tall stature, long limbs, hyperextensible joints, and lens dislocation. Echocardiography reveals aortic root dilation. His father, who had similar features, died suddenly at the age of 45. Genetic testing identifies a mutation in the FBN1 gene. What is the mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: A) Autosomal dominant
Explanation:
Marfan syndrome is caused by mutations in the FBN1 gene, which encodes fibrillin-1, a protein essential for connective tissue integrity. The inheritance is autosomal dominant because:
1. The patient inherited the disorder from his father, indicating vertical transmission (generation-to-generation).
2. Only one mutated copy of the gene is sufficient to cause the disorder.
3. Autosomal dominant disorders often exhibit variable expressivity, as seen in this family (the father’s sudden death suggests severe aortic involvement).
3. A 2-year-old girl presents with pale skin, blue eyes, a musty body odor, and developmental delays. Both parents are healthy, but they are first cousins. Biochemical analysis reveals elevated phenylalanine levels in the blood. What is the most likely mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: B) Autosomal recessive
Explanation:
This child has phenylketonuria (PKU), a metabolic disorder caused by mutations in the PAH gene. The inheritance is autosomal recessive because:
1. Both parents are asymptomatic but likely carriers, consistent with autosomal recessive inheritance.
2. Consanguinity (parents are first cousins) increases the likelihood of both parents carrying the same recessive mutation.
3. Autosomal recessive conditions typically require two mutated alleles (one from each parent) for the disorder to manifest.
4. A newborn boy presents with severe anemia, jaundice, and hepatosplenomegaly. His parents, who are first cousins, are asymptomatic. Genetic testing reveals a mutation in the HBB gene. What is the most likely mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: B) Autosomal recessive
Explanation:
This case describes beta-thalassemia major, caused by mutations in the HBB gene. The inheritance is autosomal recessive because:
1. Both parents are asymptomatic carriers of the mutation, which is typical for recessive disorders.
2. The disease manifests only when the child inherits one defective copy from each parent.
3. Consanguinity increases the likelihood of both parents carrying the same mutation.
5. A 3-year-old boy presents with developmental delay, spasticity, and self-mutilation (biting his lips and fingers). His maternal grandfather had similar symptoms before dying in adolescence. Genetic testing reveals a deficiency in hypoxanthine-guanine phosphoribosyl transferase (HGPRT). What is the mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: E) X-linked recessive
Explanation:
This case describes Lesch-Nyhan syndrome, an X-linked recessive disorder caused by HGPRT deficiency. The mode of inheritance is deduced because:
1. The patient is male, and his maternal grandfather had the condition, suggesting it is passed through female carriers.
2. X-linked recessive disorders primarily affect males, as they have only one X chromosome.
3. Females are typically asymptomatic carriers unless they inherit mutations on both X chromosomes (rare).
6. A 30-year-old woman presents with a strong family history of early-onset breast and ovarian cancer. Genetic testing reveals a mutation in the BRCA1 gene. What is the mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: A) Autosomal dominant
Explanation:
Mutations in BRCA1 are inherited in an autosomal dominant pattern because:
1. A single mutated allele is sufficient to significantly increase cancer risk.
2. The pattern of transmission involves multiple generations (vertical inheritance).
3. Both males and females can inherit and pass on the mutation, consistent with autosomal dominant inheritance.
7. A male newborn presents with prolonged bleeding after circumcision. His maternal uncle also had severe bleeding episodes and died after minor trauma. Genetic testing reveals a deficiency in factor VIII. What is the most likely mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: E) X-linked recessive
Explanation:
This case describes hemophilia A, an X-linked recessive disorder caused by factor VIII deficiency. The inheritance pattern is inferred because:
1. The patient is male, and the maternal uncle was also affected, indicating inheritance through female carriers.
2. Males are affected because they have only one X chromosome.
3. Carrier females typically do not exhibit symptoms due to having a normal X chromosome.
8. A 6-month-old boy presents with progressive developmental regression, exaggerated startle response, and a cherry-red spot on the macula. His parents are asymptomatic but are of Ashkenazi Jewish descent. Genetic testing reveals a deficiency in the hexosaminidase A enzyme. What is the mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: B) Autosomal recessive
Explanation:
This is Tay-Sachs disease, an autosomal recessive lysosomal storage disorder caused by hexosaminidase A deficiency. The mode of inheritance is autosomal recessive because:
1. Both parents are asymptomatic carriers.
2. The disorder manifests when the child inherits two defective alleles (one from each parent).
3. The higher prevalence in Ashkenazi Jewish populations suggests a founder effect.
9. A 5-year-old boy presents with difficulty walking, frequent falls, and calf muscle hypertrophy. His maternal uncle had similar symptoms and was wheelchair-bound by his teens. Genetic testing reveals a mutation in the DMD gene. What is the most likely mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: E) X-linked recessive
Explanation:
This is Duchenne muscular dystrophy, an X-linked recessive disorder caused by mutations in the DMD gene. The inheritance pattern is X-linked recessive because:
1. The disease primarily affects males.
2. Females are usually asymptomatic carriers.
3. The patient’s maternal uncle was affected, consistent with inheritance through the maternal line.
10. A 1-year-old boy presents with coarse facial features, recurrent respiratory infections, and hepatosplenomegaly. Urine analysis shows increased levels of heparan sulfate and dermatan sulfate. Both parents are asymptomatic. What is the mode of inheritance?
A) Autosomal recessive
B) Autosomal dominant
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: A) Autosomal recessive
Explanation:
This is Hurler syndrome, an autosomal recessive disorder caused by mutations in the IDUA gene. The inheritance is autosomal recessive because:
1. Both parents are asymptomatic carriers.
2. The child manifests the disorder only when inheriting two defective alleles.
3. This pattern is typical for most lysosomal storage disorders.
11. A 3-year-old boy presents with hepatosplenomegaly, failure to thrive, and pancytopenia. Bone marrow biopsy shows lipid-laden macrophages (Gaucher cells). Both parents are healthy. What is the mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: B) Autosomal recessive
Explanation:
This is Gaucher disease, an autosomal recessive lysosomal storage disorder caused by mutations in the GBA gene. The inheritance is autosomal recessive because:
1. Both parents are asymptomatic carriers.
2. The disorder manifests only when the child inherits two defective alleles.
12. A 6-month-old infant presents with progressive muscle weakness, difficulty feeding, and a floppy baby appearance. Genetic testing reveals deletions in the SMN1 gene. Both parents are asymptomatic. What is the mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: B) Autosomal recessive
Explanation:
This is spinal muscular atrophy (SMA), caused by deletions in the SMN1 gene. The inheritance is autosomal recessive because:
1. Both parents are asymptomatic carriers.
2. The disorder manifests only when the child inherits two defective alleles.
13. A 3-year-old girl presents with developmental regression, loss of purposeful hand movements, and repetitive hand-wringing behavior. She had normal development until 18 months. Genetic testing reveals a mutation in the MECP2 gene. What is the most likely mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) Mitochondrial
E) X-linked recessive
Correct Answer: C) X-linked dominant
Explanation:
This case describes Rett syndrome, an X-linked dominant disorder caused by mutations in the MECP2 gene. The inheritance pattern is X-linked dominant because:
1. It primarily affects females, as most males with the mutation do not survive to term.
2. The disorder manifests even when only one X chromosome carries the mutation.
3. Fathers cannot pass the mutation to sons, but daughters can inherit the disorder.
14. A 10-year-old girl presents with intellectual disability, a long face with prominent ears, and hyperactivity. Her mother also has a mild intellectual disability. Genetic testing reveals an expanded CGG repeat in the FMR1 gene. What is the most likely mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant
D) Mitochondrial
E) X-linked recessive
Correct Answer: C) X-linked dominant
Explanation:
This is Fragile X syndrome, an X-linked dominant disorder caused by a CGG repeat expansion in the FMR1 gene. The inheritance is X-linked dominant because:
1. Both males and females can be affected, but females often have milder symptoms due to the presence of a second X chromosome.
2. Males with the mutation are generally more severely affected.
3. The mother is mildly affected, consistent with X-linked dominant inheritance.
15. A 7-year-old boy presents with frequent fractures after minimal trauma. His sclerae appear blue, and his teeth are discolored. His father has similar symptoms. Genetic testing reveals a mutation in the COL1A1 gene. What is the mode of inheritance?
A) Autosomal dominant
B) Autosomal recessive
C) Mitochondrial
D) X-linked dominant
E) X-linked recessive
Correct Answer: A) Autosomal dominant
Explanation:
This is osteogenesis imperfecta (OI), most commonly caused by mutations in the COL1A1 or COL1A2 genes. The inheritance is autosomal dominant because:
1. The disorder is passed from father to son, confirming autosomal inheritance.
2. Only one mutated copy of the gene is sufficient to cause the disorder.
3. Autosomal dominant disorders typically show vertical transmission in families.