Hemoglobin F-Cincinnati, α2(G)γ2 41(C7) Phe→Ser in a newborn with cyanosis

M. Kohli-Kumar, Theodore Zwerdling, D. L. Rucknagel

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

A term infant presented with mild cyanosis without evidence of hypoxia. Cardiopulmonary disease, polycythemia, and methemoglobinemia were excluded. Standard hemoglobin electrophoresis, including isoelectric focusing, were normal. However, by reverse-phase C4 HPLC, an abnormal globin chain was detected. Analysis of tryptic peptides and amino acid sequence showed that the patient had an amino acid substitution Phe→Ser at residue 41 (C7) in the (G)γ chain. This was confirmed by DNA sequencing that demonstrated a point mutation at the expected site in exon 2 of the (G)γ gene, accounting for the appropriate change in the codon. This substitution, hemoglobin F-Cincinnati, α2γ2 41(C7) Phe→Ser, not previously described, presumably decreased oxygen affinity of the hemoglobin. This substitution is very near the heme group and the α1 β2 interface and, hence, in a crucial area of the globin chain. Abnormalities of γ globin chains tend to be overlooked due to their transient presence and trivial clinical symptomatology, or due to 'in utero' selection when physiologically abnormal. Mutant hemoglobins with altered oxygen affinity should be included in the differential diagnosis of newborns presenting with cyanosis, in whom all common causes have been excluded.

Original languageEnglish (US)
Pages (from-to)43-47
Number of pages5
JournalAmerican Journal of Hematology
Volume49
Issue number1
StatePublished - 1995
Externally publishedYes

Fingerprint

Cyanosis
Globins
Hemoglobins
Newborn Infant
Oxygen
Methemoglobinemia
Polycythemia
Isoelectric Focusing
Amino Acid Substitution
DNA Sequence Analysis
Point Mutation
Codon
Electrophoresis
Amino Acid Sequence
Exons
Differential Diagnosis
High Pressure Liquid Chromatography
Peptides
Genes
hemoglobin F-Cincinnati

Keywords

  • Cyanosis
  • Fetal hemoglobin mutation
  • Hemoglobin
  • Infant
  • PCN

ASJC Scopus subject areas

  • Hematology

Cite this

Hemoglobin F-Cincinnati, α2(G)γ2 41(C7) Phe→Ser in a newborn with cyanosis. / Kohli-Kumar, M.; Zwerdling, Theodore; Rucknagel, D. L.

In: American Journal of Hematology, Vol. 49, No. 1, 1995, p. 43-47.

Research output: Contribution to journalArticle

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