Medical Emergencies · patient case question
Sickle cell anaemia results from which type of mutation?
Patient case: A painful crisis in a young adult
demo: 24-year-old male
chief: Severe generalised bone pain, worst in the mandible and long bones, for two days.
history: Sickle cell anaemia diagnosed in infancy. Two hospital admissions in the past year for painful crises. He became dehydrated at a football match the day before this episode began.
meds: Hydroxyurea, folic acid.
findings: Afebrile, tachycardic. Panoramic radiograph shows a stepladder trabecular pattern with enlarged marrow spaces and generalised radiolucency of the jaws.
Show answer and explanation
Correct answer: C. Missense mutation
- A. A frameshift results from insertion or deletion of a number of bases not divisible by three, scrambling everything downstream. The sickle mutation is a clean single substitution.
- B. A silent mutation changes the base but not the encoded amino acid, thanks to codon redundancy, so it produces no phenotype.
- C. Correct. A single base substitution of adenine for thymine in the sixth codon of the beta-globin gene replaces glutamic acid with valine. One amino acid is exchanged for a different one, which is the definition of a missense mutation. Losing that negative charge lets deoxygenated haemoglobin S polymerise.
- D. A nonsense mutation converts a codon into a stop codon and truncates the protein. Some beta-thalassaemia alleles arise this way, but sickle cell disease does not.
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