WBR0218

Author	PageAuthor::William J Gibson
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 ER by her father. The girl is continuously crying in pain. She refuses to bear weight on her feet, and attempts to avoid the physician inspecting her feet or hands manually. Her hands and feet are swollen, warm and tender to palpation. X ray of the child’s hands and feet revealed no bony abnormalities but were consistent with swelling of the surrounding tissues. Further questioning reveals that the child had suffered from diarrhea one day prior to being admitted to the ER. Intravenous saline and naproxen, are administered to the patient and she recovers the following day. 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. Educational Objective: Sickle cell anemia is caused by a missense mutation in the beta-globin gene. References: First Aid 2012 page 386]]
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
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