A family with multiple mutations and sequence variations in the alpha- and beta-globin gene clusters

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Laboratory diagnostics for hereditary hemoglobin disorders are typically straightforward but can present challenges.
• Complex cases require advanced molecular analysis for accurate diagnosis.

Purpose of the Study:

• To describe a family with multiple, co-existing mutations and sequence variations in alpha- and beta-globin gene clusters.
• To illustrate the diagnostic challenges posed by complex genetic backgrounds in hemoglobinopathies.

Main Methods:

• Utilized automated cell counters for hemocytometry.
• Performed hemoglobin variant analysis via cation-exchange High-Performance Liquid Chromatography (HPLC).
• Employed Polymerase Chain Reaction (PCR) and DNA sequencing to identify globin gene mutations.

Main Results:

• Identified a heterozygous Hemoglobin C (HbC) mutation, a beta-thalassemia mutation (-90C>T), and heterozygous alpha-thalassemia (-alpha(-3.7)/alpha alpha).
• Discovered three distinct gamma-globin sequence variations in the proposita.
• A total of ten different mutations were detected across the family's globin genes.

Conclusions:

• Molecular analysis is crucial for clarifying complex hemoglobin variant findings, such as low HbA1 levels.
• Understanding the molecular basis of hematological parameters is essential for accurate patient diagnosis and counseling.
• This family case underscores the importance of comprehensive genetic evaluation in diagnosing hemoglobin disorders.