Hemoglobin Loves Park [β68 (E12) Leu→Phe]: Report of five cases including one originating from a de novo mutation

Abstract

Hemoglobin (Hb) Loves Park [b68 (E12) Leu?Phe] was identified in a 2-year-old Portuguese boy with anemia, microcytosis, and hypochromia. This Hb variant was detected by isoelectric focusing and quantified by reverse-phase high-performance liquid chromatography (HPLC) (48.4%), and the DNA mutation was identified by HBB (b-globin gene) sequencing. Hematological and biochemical analyses performed on his parents revealed normal hematological parameters and normal hemoglobin and globin chain profiles. DNA sequence analysis of the HBB gene of both parents showed the absence of the Hb Loves Park mutation. Study of the haplotypes in the b-globin gene cluster confirmed parenthood. Moreover, paternity was confirmed by the study of nine short tandem repeats (STRs) and four variable-number tandem repeat (VNTRs) loci. The most likely explanation for these results is that the Hb Loves Park mutation has occurred de novo in this family. The original American cases of Hb Loves Park, from a family of Italian origin, which were never published, as well as two additional cases, are also included in this report. Functional studies revealed that Hb Loves Park is stable and has a decreased oxygen affinity. Am. J. Hematol. 81:256-261, 2006. V V C 2006 Wiley-Liss, Inc.

Non-S Sickling Hemoglobin Variants: Historical, Genetic, Diagnostic, and Clinical Perspectives

“… 28 Hb Jamaica Plain may thus be responsible for sporadic and inexplicable cases of clinically severe VO symptoms in persons with presumed ‘HbS trait’ if only basic electrophoretic and chromatographic techniques are used for diagnosis. 28 It is noteworthy that the second mutation (βLeu68Phe) was previously reported as an isolated finding in Hb Rockford, 62 now known as Hb Loves Park, 63 which is associated with low oxygen affinity. Consequently, Hb Jamaica Plain is functionally a low oxygen affinity variant (as is the case with Antilles, HbS-Cameroon, and HbS-South End) characterized by a marked decrease in oxygen affinity that is even lower than that of HbS Antilles.…”