A new Variant, Hb Muscat [α<sub>2</sub>β<sub>2</sub>32(B14)Leu→val] Observed in Association With Hb S in an Arabian Family

Hematological and hemoglobin (Hb) data are presented for numerous patients with compound heterozygosities for different β chain variants and for a β chain variant with different β-thalassemia (β-thal) alleles. Considerable variations, which result from the type of β chain variant and β-thal mutation, can be noted. The comparison again emphasizes the importance of determining the diagnoses at the molecular level to aid the physician in the management of patients with different combinations of abnormalities. Simplification and commercialization of modern technology may make the introduction of this approach in some clinical chemistry laboratories possible.

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Two missense mutations in the beta-globin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine-->glutamine; 98 [FG5] valine-->methionine).

Coleman

Lu²,

Smith³

et al. 1995

J. Clin. Invest.

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We studied the molecular basis of transfusion-dependent hemolytic anemia in an infant who rapidly developed the phenotype of .8thalassemia major. DNA sequence of one /3-globin gene of the proband revealed two mutations, one for the moderately unstable hemoglobin (Hb) Koln and another for a novel codon 32 cytosine-thymidine-guanine-cytosineadenine-guanine transversion encoding a leucine-glutamine mutation. A hydrophilic glutamine residue at /332 has an uncharged polar side chain that could potentially distort the B helix and provoke further molecular instability. This new hemoglobin was called Hb Medicine Lake. Biosynthesis studies showed a deficit of j8-globin synthesis with early loss of /3-globin chains. An abnormal unstable hemoglobin, globin chain, or tryptic globin peptide was not present, demonstrating the extreme lability of this novel globin. Hb Medicine Lake mRNA was present, but an aberrantly spliced message was not. Absence of an abnormal .8-globin gene in the mother makes it likely that a de novo mutation occurred in the proband. The molecular pathogenesis of Hb Medicine Lake illustrates a mechanism whereby the phenotype of a genetic disorder, like the mild hemolytic anemia associated with a hemoglobinopathy, can be modulated by a coincident mutation in the same gene. (J. Clin. Invest. 1995. 95:503-509.)

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A new Variant, Hb Muscat [α₂β₂32(B14)Leu→val] Observed in Association With Hb S in an Arabian Family

Cited by 8 publications

References 16 publications

A new Unstable α2‐Globin Gene Variant: Hb Chartres [α33(B14)Phe→Ser]

A new Unstable α2‐Globin Gene Variant: Hb Chartres [α33(B14)Phe→Ser]

Combinations of β chain abnormal hemoglobins with each other or with β-thalassemia determinants with known mutations: influence on phenotype

Two missense mutations in the beta-globin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine-->glutamine; 98 [FG5] valine-->methionine).

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A new Variant, Hb Muscat [α2β232(B14)Leu→val] Observed in Association With Hb S in an Arabian Family

Cited by 8 publications

References 16 publications

A new Unstable α2‐Globin Gene Variant: Hb Chartres [α33(B14)Phe→Ser]

A new Unstable α2‐Globin Gene Variant: Hb Chartres [α33(B14)Phe→Ser]

Combinations of β chain abnormal hemoglobins with each other or with β-thalassemia determinants with known mutations: influence on phenotype

Two missense mutations in the beta-globin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine-->glutamine; 98 [FG5] valine-->methionine).

Contact Info

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A new Variant, Hb Muscat [α₂β₂32(B14)Leu→val] Observed in Association With Hb S in an Arabian Family