Hb Toranomon [beta 112(G14)Cys-->Trp]: a new unstable electrophoretically silent hemoglobin

Area of Science:

• Hematology
• Biochemistry
• Molecular Biology

Background:

• Hemoglobin variants can be silent or unstable, impacting red blood cell function.
• Accurate identification of hemoglobinopathies is crucial for clinical diagnosis and genetic counseling.
• High-performance liquid chromatography (HPLC) is a key technique for hemoglobin analysis.

Observation:

• A silent and unstable hemoglobin variant, designated Hb Toranomon, was detected during a routine HbA1c assay in an apparently healthy Japanese male.
• Initial analyses including isoelectric focusing and globin chain chromatography showed no abnormalities.
• The isopropanol precipitation test yielded a positive result, indicating potential instability.

Findings:

• Amino acid analysis and protein sequencing identified a Cys-->Trp substitution at beta-chain position 112.
• cDNA sequencing confirmed the nucleotide change from TGT to TGG at the corresponding codon.
• The beta/alpha globin biosynthesis ratio was normal (1.00), suggesting no significant imbalance in subunit production.

Implications:

• Hb Toranomon represents a newly characterized hemoglobinopathy with potential clinical relevance despite its silent nature.
• This case underscores the utility of combining multiple analytical methods, including HPLC and protein sequencing, for comprehensive hemoglobin variant characterization.
• Further studies are warranted to elucidate the precise mechanisms of instability and potential clinical manifestations of Hb Toranomon.