Masking of a β-thalassemia determinant by a novel δ-globin gene defect [Hb A2-Saurashtra or δ100(G2)Pro→Ser; HBD:...

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Beta-thalassemia (β-thal) molecular basis is known, but delta-thalassemia (δ-thal) mutations are less characterized.
• δ-thal is asymptomatic but coinheritance with heterozygous β-thal can cause misdiagnosis, particularly in high-prevalence areas.
• The association of β- and δ-globin mutations is uncommon in India, potentially complicating diagnosis and genetic counseling for β-thal.

Purpose of the Study:

• To investigate borderline Hemoglobin A2 (Hb A2) levels in two Indian families.
• To identify novel genetic mutations causing δ-thalassemia and β-thalassemia.
• To emphasize the importance of δ-globin gene analysis in β-thal screening programs.

Main Methods:

• Molecular screening for thalassemia mutations.
• Analysis of hemoglobin variants, including Hb A2 levels.
• Genetic sequencing to identify novel mutations.

Main Results:

• Two families from the Koli Community in Gujarat, India, presented with borderline Hb A2 levels.
• A novel δ-globin gene mutation at codon 100 (C > T) was identified.
• This δ-thal mutation was linked to a previously unreported 5 bp deletional β-thal mutation affecting the polyadenylation site.

Conclusions:

• δ-globin gene analysis is crucial during β-thal screening to prevent false-negative results in at-risk couples.
• Incomplete diagnosis of borderline or normal Hb A2 levels can lead to the birth of individuals with β-thalassemia major (β-TM).
• Accurate molecular diagnosis has significant implications for prenatal diagnosis and genetic counseling in thalassemia prevention programs.