Hb Amsterdam-A1 [α32(B13)Met→Ile; HBA1: c.99G>A]: A Hyperunstable Variant Due to a New Mutation on the α1 Gene

Patients with hyperunstable α chain variants usually present with a thalassemic, rather than hemolytic, phenotype. Electrophoretic, ion exchange and reverse phase separations usually fail to detect the variant and when DNA sequencing identifies a 'silent' substitution it is usually presume...

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Bibliographic Details
Published in:Hemoglobin 2017-03, Vol.41 (2), p.140-143
Main Authors: Brennan, Stephen O., Wang, Darrell, Horridge, Mark, Sheen, Campbell R.
Format: Article
Language:English
Subjects:
Adult
Female
Hemoglobins, Abnormal - chemistry
Hemoglobins, Abnormal - genetics
Humans
hyperunstable hemoglobin (Hb)
isopropanol test
mass spectrometry (MS)
Mutation
Protein Stability
α-Thalassemia
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Summary:Patients with hyperunstable α chain variants usually present with a thalassemic, rather than hemolytic, phenotype. Electrophoretic, ion exchange and reverse phase separations usually fail to detect the variant and when DNA sequencing identifies a 'silent' substitution it is usually presumed to be hyperunstable. We report the identification of such a variant, α32(B13)Met→Ile; HBA1: c.99G>A, arising from a new mutation on the α1 gene. The hemoglobin (Hb) was unequivocally detected by the isopropanol stability test and confirmed as hyperunstable by mass spectrometry (MS) of the precipitate and lysate, which showed proportions of 55% and 2.5% of α chains, respectively. The instability appears to be driven by perturbation of globin-heme, and possibly α1β1 subunit, interactions.
ISSN:0363-0269
1532-432X
DOI:10.1080/03630269.2017.1311911