Hemoglobin Ozieri: a new alpha-chain variant (alpha 71(E20)Ala-->Val). Characterization using FAB- and electrospray-mass spectrometric techniques.

Abstract

A new silent hemoglobin variant, Hb Ozieri (alpha 71(E20)Ala-->Val), was observed in five apparently unrelated newborn babies during a screening for hemoglobinopathies on the island of Sardinia. This asymptomatic variant was detected by means of isoelectric focusing (IEF), isolated using IEF in an immobilized ultranarrow pH-gradient and characterized at the structural level using FAB- and electrospray-mass spectrometric techniques. A Val for Ala substitution was unambiguously detected at position 71 of the alpha-globin chain. This substitution indicates that a C to T transition occurred in the GCG codon for Ala which contains one of the 35 unmethylated CpG dinucleotides of the alpha-globin gene. This observation brings the number of variants due to a mutation in the alpha-globin gene CpGs (the third instance of a silent mutation) to 13 and raises the possibility that unmethylated CpGs might be hotspots for mutations as the methylated ones.

• Authors: P Ferranti, A Parlapiano, A Malorni, P Pucci, G Marino, G Cossu, L Manca, B Masala
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1162 Issue 1-2 Pg. 203-8 (Mar 05 1993) ISSN: 0006-3002 [Print] Netherlands
• PMID: 8448185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hemoglobins, Abnormal
• hemoglobin Ozieri
• Globins
• Valine
• Alanine

Topics

• Alanine
• Base Sequence
• Fetal Blood
• Globins (genetics)
• Hemoglobinopathies (blood)
• Hemoglobins, Abnormal (chemistry, genetics)
• Humans
• Infant, Newborn
• Isoelectric Focusing
• Italy
• Mass Spectrometry (methods)
• Mutation
• Valine