Expression Differences of Abnormal Hemoglobin New York in Infants, Children and Adults, and Analysis of Clinical Phenotypes and Genotypes in Combination with Thalassemia

The study investigated expression differences of Hb New York (HBB:c.341T > A) across infants, children, and adults, and analyzed the clinical phenotypes and genotypes when co‑inherited with thalassemia. We retrospectively reviewed 317 cases of Hb New York carriers, assessing hematological parameters, hemoglobin electrophoresis, and genetic testing results. All samples carried the HBB:c.341T > A mutation, including 266 heterozygotes (192 adults, 74 infants and children) and 51 compound heterozygotes with thalassemia. Adult heterozygotes exhibited normal hematological phenotypes, with Hb New York levels of 43.6 ± 2.9%. Compound heterozygosity with α-thalassemia silent carrier showed normal or near-normal red blood cell parameters (Hb New York: 38.8 ± 2.9%), whereas co-inheritance with α-thalassemia trait caused microcytosis, hypochromia, and mild anemia (Hb New York: 35.2 ± 2.4%). Co-inheritance with β-thalassemia mutations (βCD17, βCD71-72, HBB:c.91A > G) presented mild β-thalassemia traits (Hb New York > 91.6%), and combination with Hb J-Bangkok showed normal phenotypes. The Hb New York level in newborns gradually increased over the months. The content of Hb New York in heterozygotes was 4.8 ± 2.0%, and when combined with thalassemia gene mutations, it was 5.1 ± 2.3%, indicating similar Hb New York levels between the two groups. We conclude that Hb New York levels are positively correlated with normal α-globin chain expression but inversely correlated with normal β-globin chain expression. Hb New York heterozygotes have normal hematological phenotype; compound heterozygosity with an α-thalassemia silent carrier causes minimal hematological alterations, whereas combination with other thalassemias induces anemia of variable severity dependenting on the thalassemia subtype.