WBR0218
| Author | [[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics |
| Sub Category | SubCategory::Hematology, SubCategory::Vascular, SubCategory::General Principles |
| Prompt | [[Prompt::A 4-year-old African-American girl is brought to the emergency department by her father. The girl is continuously crying in pain. Her hands and feet are swollen and painful. On physical examination, the patient's extremities are warm and tender to light palpation. X ray of the patient's hands and feet reveals tissue swelling but no bony abnormalities. Further questioning reveals that the child is the product of a consanguineous marriage. The patient is then admitted for management with intravenous saline and analgesic agents. Which of the following genetic alterations is most likely responsible for this patient’s condition?]] |
| Answer A | AnswerA::Nonsense mutation |
| Answer A Explanation | [[AnswerAExp::Sickle cell anemia is caused by a missense mutation in the beta-globin gene. Nonsense mutations refer to the inappropriate insertion of a stop codon, resulting in a shortened non-functional protein. An example of a disease associated with nonsense mutation is Duchenne muscular dystrophy.]] |
| Answer B | AnswerB::Mosaic mutation |
| Answer B Explanation | AnswerBExp::Sickle cell anemia is caused by a missense mutation in the beta-globin gene. Mosaicism denotes the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg. |
| Answer C | AnswerC::Missense mutation |
| Answer C Explanation | AnswerCExp::Sickle cell anemia is caused by a missense mutation in the beta globin gene. |
| Answer D | AnswerD::Splice-site mutation |
| Answer D Explanation | [[AnswerDExp::Sickle cell anemia is caused by a missense mutation in the beta globin gene. Splice site mutations interfere with the normal splicing of pre-mRNA to mature mRNA, resulting in a non-functional protein product. An example of a disorder associated with splice-site mutations is beta-thalasemmia.]] |
| Answer E | AnswerE::Imprinting |
| Answer E Explanation | AnswerEExp::Imprinting refers to the allele specific expression of a gene or set of genes. An example of a disorder associated with imprinting is Prader-Willi syndrome. |
| Right Answer | RightAnswer::C |
| Explanation | [[Explanation::The child in this vignette is suffering from dactylitis, a common complication of sickle cell anemia. Sickle cell anemia is a hereditary blood disorder, characterized by red blood cells that assume an abnormal, rigid, sickle shape particularly when exposed to stress or hypoxia. The sickling occurs because of a mutation in the haemoglobin gene. Vaso-occlusive crises are caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischemia, pain, necrosis and often organ damage. In this case, the patient is experiencing vaso-occlusive crises of the hands and feet known as dactylitis.
Sickle-cell anaemia is caused by a point mutation in the β-globin chain of haemoglobin, causing the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position. Individuals homozygous for the mutated beta globin gene, termed HbS, have sickle cell anemia. Those who are heterozygous for the mutated gene have sickle cell trait, which does not display the severe symptoms of sickle cell anemia. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Anemia, WBRKeyword::Sickle cell anemia, WBRKeyword::Sickle cell, WBRKeyword::Sickle cell disease, WBRKeyword::Genetics, WBRKeyword::Mutation, WBRKeyword::Hematology, WBRKeyword::Blood |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |