Hemoglobin Jamaica plain--a sickling hemoglobin with reduced oxygen affinity

Area of Science:

• Genetics
• Molecular Biology
• Hematology

Background:

• Newborn screening typically identifies sickle cell trait, a generally benign condition.
• Symptomatic sickle cell disease (SCD) usually presents with homozygous or compound heterozygous mutations.
• Mild hypoxemia can exacerbate SCD symptoms.

Observation:

• A baby girl presented with symptomatic SCD despite a sickle cell trait diagnosis.
• Genetic analysis revealed a novel double mutation on the paternal beta globin allele.
• The patient's hemoglobin exhibited severely reduced oxygen affinity.

Findings:

• A novel hemoglobin variant, termed "hemoglobin Jamaica Plain," was identified.
• This variant results from a combination of the sickle mutation (betaGlu6Val) and a second mutation (betaLeu68Phe).
• Structural modeling suggests the double mutation destabilizes the oxy conformation of hemoglobin.

Implications:

• This case expands the understanding of genetic determinants in sickle cell disease.
• Novel hemoglobin variants can cause severe phenotypes even in heterozygotes.
• Identifies a potential molecular mechanism for sickling under specific oxygen conditions.