Hematological Observations on Arabian SS Patients with a Homozygosity or Heterozygosity for a β^SChromosome with Haplotype #31

Abstract

Hematological and hemoglobin composition data are presented for seven Arabian SS patients with mild disease and with high Hb F levels varying between 21 and 34%. Four patients were homozygous for a beta S chromosome with a specific haplotype (#31). The data for these four patients were similar to those for three other SS patients (and for five patients reported earlier, Ref. 2) who were heterozygous for the same beta S chromosome (#31) and for a beta S chromosome with another haplotype (mainly #19). These data offer additional evidence indicating that the increased gamma chain production is specific for the beta S chromosome with haplotype #31. The similarities in hematological data and Hb F levels between these two groups of SS patients and the normal Hb F value in Hb S heterozygotes with beta S chromosome (#31) support the suggestion that the increased Hb F production mainly occurs in response to the anemia of the sickle cell disease.

Original Research: A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease

“…Historically, five major b-haplotypes, including Senegal, Benin, Central African Republic (Bantu), Cameroon, and Asian (Indian/Saudi-Arabian), 35,54,[73][74][75][76] have been defined in African SCD populations; however, these haplotypes are not predictive of HbF levels. We recently published data demonstrating that b-haplotypes generated using traditional methods such as restriction fragment length polymorphisms are insufficient to define the genomic structure in the HBB locus.…”

Minireview: Multiomic candidate biomarkers for clinical manifestations of sickle cell severity: Early steps to precision medicine

“…The Bantu and Benin haplotypes have been associated with low HbF levels and increased severity of clinical manifestations in sickle cell patients 3,35 compared with the Senegal and Arab-Indian haplotypes with higher HbF and a milder disease phenotype. 36,37 However, these haplotypes are not consistently predictive of clinical severity of SCA patients.…”

Comparison of the Relative Quantities of γ-mRNAs and Fetal Hemoglobin in SS Patients with Different Haplotypes

“…These ratios are defined in more detail in this study as is shown in figure 2; homozygotes for haplotypes 3 or 31 have G γ values of 70–76%; those for type 19, 20, and for types 19 + 20 have G γ values of 36–53%, while compound heterozygotes for types 3 and 19 and for 3 and 20 have G γ levels from 54 to 73%, distinctly lower than the values for haplotype 3 homozygotes. The observed differences have been explained based on the presence or absence of the C→T mutation at position –158 ( G γ) (T for β S haplotypes 3 and 31; C for all others) [11, 14, 15, 16, 17]. The Mor haplotype appears to be unique: the 1 SS patient with a homozygosity for this haplotype has a G γ value of less than 20% and the 2 with the 19/Mor haplotype combination have values of 29.8 and 32.8%, intermediate between the values for patients with haplotypes 19/19 and Mor/Mor.…”