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25 Cards in this Set
- Front
- Back
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Cause of Hb Gun Hill.
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Hb Gun Hill (AD)
Caused by small deletion |
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Mechanism of Hb Gun Hill.
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slipped mispairing during DNA replication within same gene => 15 base pair in-frame deletion in beta globin => loss of 5 amino acids
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Change in polypeptide -- Hb Hyde Park.
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His => Tyr(92)
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Clinical feat. of pts with Hb Hyde Park?
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Asymptomatic Cyanosis b/c of the Hb resulting from the polypsptide change (His=>Tyr) is not used by methemeoglobin reductase.
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This hemoglobinopathy results in polycythemia. What is the mechanism?
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Asp → Asn(99)
Mutation locks hemoglobin into relaxed structure, causeing increased O2 affinity and impaired deliver of O2 to tissues (aka polycythemia). |
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Asn → Thr(102); This mutation inhibits formation of relaxed structure, thus lower affinity for O2 → cyanosis (asymptomatic). What Hemoglobinopathy am I?
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Hb Kansas (AD)
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How is the O2 affinity altered if a pt presents with Hd Tak (AR)?
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Increased O2 affinity b/c increased the length of B-globin chain
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Clinical symptoms of Homozygous Hb E patients?
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Homozygotes => asymptomatic with mild anemia
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δ globin gene deleted but fusion gene δβ present => Hb _____.
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δ globin gene deleted but fusion gene δβ present => Hb Lepore
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Both δ globin gene and fusion gene βδ present => Hb ______ => Example: Hb Miyada
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Both δ globin gene and fusion gene βδ present => anti-Lepore => Example: Hb Miyada
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Thalassemias are cx by?
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Disorders of Hb Synthesis
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α Thalassemia – the synthesis of α chain is ______ or absent, while β chain synthesis is _________.
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α Thalassemia – the synthesis of α chain is decreased or absent, while β chain synthesis is normal
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In β Thalassemia – the β chain synthesis is ________ or absent; α chain synthesis is _______
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In β Thalassemia – the β chain synthesis is decreased or absent; α chain synthesis is normal
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NOTE: Defect in production of hemoglobin ==> hypochromic, microcytic anemia
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NOTE: In Thalassemias the chain rpoduced in excess comtribute to the formation of Heinz bodies and consequent hemolytic anemia
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What is the most severe form of a-thalassemia?
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Hb-Barts (Hydrops Fetalis).
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-Microcytic hypochromic anemia
-Ineffective erythropoeisis -Marrow hyperplasia and extramedullary erythropoeisis -Elevated HbA2 -Increased level of HbF -chipmunk facies What type of thalassemia am I? |
Beta-Thalassemias
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α-Thalassemias vs β-Thalassemias
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In contrast to α-Thalassemias, β-Thalassemias are mostly caused by single base-pair substitutions
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Three most common mutations leading to β-Thalassemia are:
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1: splice junction mutations -
mutations in 5’ intron donor or 3’ intron acceptor sites 2: Intron mutations - Intron mutations that activate cryptic splice site 3: Exon mutations that affect splicing - exon mutation that affect splicing by activating cryptic splice sites (e.g. Hb E) |
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Nonfunctional mRNAs and Defects in capping and tailing of mRNA are other causes of what type of thalassemia?
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B-Thal.
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In complex thalassemias what happens if LCR is deleted?
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If LCR is removed, all genes of the cluster may remain intact but they are not expressed
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What are the 7 Hb's that are caused by single nucleotide substitutions?
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1. Hb S
2. Hb C 3. Hb Hammersmith 4. Hb Hyde Park 5. Hb Kempsey 6. Hb Kansas 7. Hb E |
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Unequal crossing over causes these three Hb's.
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1. Hb Gun Hill
2. Hb Lepore 3. Hb Anti-Lepore |
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Frameshift mutation causes AR this Hb.
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Hb Tak
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What are the 6 AR Hb's?
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1. Hb S
2. Hb C 3. Hb Tak 4. Hb E 5. Hb Lepore 6. Hb Anti-Lepore |
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What are the 5 AD Hb's?
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1. Hb Hammersmith
2. Hb Gun Hill 3. Hb Kansas 4. Hb Kempsey 5. Hb Hyde Park |
