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Hb Olivet (HBA1: C.40G > A; p.Ala14Thr), a Novel Silent Hemoglobin Variant in Two Families of Distinct Origin
Cornelis L Harteveld1, Serge Pissard2, Anna M H Korver3
1a Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics , Leiden University Medical Center (LUMC) , Leiden , the Netherlands.
Insights
A novel hemoglobin (Hb) variant, Hb Olivet, behaves as a silent Hb. Its clinical presentation, potentially influenced by iron levels, ranges from asymptomatic to mild microcytic anemia in carriers.
Area of Science:
- Hematology
- Genetics
- Molecular Biology
Background:
- Hemoglobin (Hb) variants can impact red blood cell characteristics and oxygen transport.
- Silent Hb variants present diagnostic challenges due to minimal or absent phenotypic expression.
Purpose of the Study:
- To characterize a novel hemoglobin variant, Hb Olivet [α13(A11)Ala→Thr], identified in two families.
- To describe the genotype-phenotype correlation and clinical behavior of Hb Olivet carriers.
Main Methods:
- Hemoglobin analysis using capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC).
- Clinical evaluation of affected individuals, including red blood cell indices and iron status.
- Genetic analysis to confirm the novel Hb variant.
Main Results:
- Hb Olivet was identified as a novel silent Hb variant.
- Clinical manifestations in carriers varied, with some showing borderline or normal red blood cell indices and others presenting with mild microcytic hypochromic anemia.
- Iron depletion appeared to be a significant factor influencing the phenotype in carriers.
Conclusions:
- Hb Olivet is a silent hemoglobinopathy with variable expressivity.
- Iron status plays a crucial role in the phenotypic presentation of Hb Olivet carriers.
- Further investigation into genotype-phenotype correlations in hemoglobinopathies is warranted.
Abstract:
We report two families, members of which are carriers of a novel hemoglobin (Hb) variant that was named Hb Olivet [α13(A11)Ala→Thr (α1) (GCC > ACC); HBA1: c.40G > A; p.Ala14Thr]. The analysis of these cases allowed a clear description of this anomaly that behaves as a silent Hb. In the first family, of Portuguese ethnicity living in France, the proband, a 24-year-old male and his 57-year-old mother, both appeared to be carriers. The son presented with borderline mean corpuscular volume (MCV), while the mother was normocytic and normochromic. Hemoglobin separation on capillary electrophoresis (CE) was normal, while a slightly asymmetric peak was observed on high performance liquid chromatography (HPLC). In a second family, originally from Surinam but living in The Netherlands, the proband, a 6-year-old girl, showed a mild microcytosis at low ferritin levels. The abnormal Hb was inherited from the mother who was clearly iron depleted, was not present in the sister and brother of the proband. The microcytic hypochromic anemia was only shown in two out of a total of four carriers. It therefore seems likely that iron depletion is causative as two carriers are completely normal. Characterization and genotype/phenotype correlation are briefly described.