Hemoglobin Loves Park [beta68 (E12) Leu-->Phe]: report of five cases including one originating from a de novo mutation.
Hemoglobin (Hb) Loves Park [beta68 (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 (beta-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 beta-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.
Ferreira
Cristina
C
Laboratório de Biologia Molecular, Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA), Lisbon, Portugal.
Hoyer
James D
JD
Miranda
Armandina
A
Picanço
Isabel
I
Almendra
Vanda
V
Seixas
Maria Teresa
MT
Almeida
Teresa
T
Romão
Luísa
L
Faustino
Paula
P
D019943:Amino Acid Substitution; D000747:Anemia, Hypochromic / Q000097:blood / Q000235:genetics*; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D005810:Multigene Family / Q000235:genetics; D017354:Point Mutation; D020080:Tandem Repeat Sequences / Q000235:genetics; D014481:United States
D006455:Hemoglobins, Abnormal; C510330:hemoglobin Loves Park