A Variable Clinical Presentation of Hemoglobin City of Hope

Dafna Brik Simon, Dvora Filon, Vardiella Meiner, Tanya Krasnov, Sharon Noy-Lotan, Orly Dgany, Oded Gilad, Tracie Goldberg, Shai Izraeli, Joanne Yacobovich, Hannah Tamary, Orna Steinberg-Shemer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Hemoglobin City of Hope (Hb-COH), NC_000011.9(NM_000518.5):c.208G > A; NP_000509.1:p.(Gly70Ser), has rarely been described. The presentation ranges from asymptomatic heterozygosity to significant anemia in patients carrying an additional pathogenic variant in β-globin. To elucidate the clinical spectrum of Hb-COH, we analyzed 31 individuals carrying the variant, including, for the first time, homozygous individuals. Seven patients who were compound heterozygous for Hb-COH and an additional variant in β-globin, presented with mild-to-severe microcytic anemia and elevated hemoglobin-A2. Three (43%) of these also had elevated fetal hemoglobin, but none required blood transfusions. Seven patients coinherited Hb-COH with an -α3.7-deletion (NG_000006.1:g.34247_38050del), their presentation ranged from mild microcytic anemia to normal blood counts. Three homozygous and 14 heterozygous individuals for Hb-COH had normal blood counts. Most Hb-COH alleles whose origin was traceable were from Ashkenazi Jews (70.4%). To conclude, while isolated Hb-COH appears asymptomatic even in the homozygous state, it may cause significant anemia when coinherited with an additional pathogenic variant in β-globin. Understanding the full impact of Hb-COH is crucial for optimal patient management and for genetic counseling.

Original languageEnglish
JournalClinical Genetics
DOIs
StateAccepted/In press - 2024

Keywords

  • City of Hope
  • anemia
  • genetics
  • thalassemia

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