Hemoglobin North Shore: A Variant Hemoglobin Associated With the Phenotype of jI-Thalassemia

SYNDROMES are characterized by the unequal production of structurally normal globin subunits.’ Very few mutations of hemoglobin structure mimic the clinical phenotype of thaIassemia. The Lepore i5fl hemoglobins’2 and the elongated a-chain termination codon mutants3 are structural variants that are poorly synthesized, leading to erythrocyte microcytosis and conditions similar to heterozygous (3or a-thalassemia. Although some unstable hemoglobins are associated with elevated HbA2, microcytosis or low mean cell hemoglobin is rare.67 HbE is a common f3-chain variant associated with microcytosis due to the “thalassemic” nature of the fl’-gene.t ‘#{176} Hb Indianapolis is a remarkably unstable variant that produces the phenotype of severe fl-thalassemia.”2 A recently described unstable achain variant, Hb Quong Sze, produces the phenotype of a-thalassemia.’3’4 In this study we report clinical, functional, and biosynthetic investigations on a kindred with Hb North Shore [i9134 (Hl2) glutamic acid].’5”6 This mildly unstable hemoglobin is associated with a heterozygous 3-thalassemia phenotype that is most likely due to impaired synthesis of the variant globin chain.