HBD – Delta-beta Thalassemia

Two unrelated individuals homozygous for large deletions encompassing the HBD gene and the adjacent β-globin locus present in infancy with severe microcytic, hypochromic anemia consistent with Delta-beta Thalassemia. Autosomal recessive inheritance was confirmed by heterozygous deletion status in each parent, and diagnosis was established by direct globin chain quantitation using LC-MS/MS and validated by multiplex ligation-dependent probe amplification (MLPA) in both families (PMID:38212249).

A hemoglobin-deficit mouse model with homozygous hbd deletion exhibits severe microcytic anemia and a late block in erythroid differentiation following bone marrow transplantation, recapitulating the human phenotype and implicating a recessive bone marrow–intrinsic defect in HBD-related globin synthesis (PMID:9292544). These functional studies support haploinsufficiency of δ-globin in the pathogenesis of delta-beta thalassemia.

Key take-home: HBD deletions produce a clinically recognizable autosomal recessive delta-beta thalassemia amenable to precise protein-based and genetic diagnostics for early intervention.

References

• Proteomics | 2024 | Identification of a rare [GγAγŽ0]-thalassemia using tandem mass spectrometry. PMID:38212249
• Blood | 1997 | The hemoglobin-deficit mouse: analysis of phenotype and hematopoiesis in the transplant model. PMID:9292544

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