Elevated Hb A is Not Always Indicative of β-Thalassemia.

Hb A levels are usually high in carriers of β-thalassemia (β-thal). These levels also provide a sensitive marker for the identification of hemoglobin (Hb) variants. In this study, we aimed to examine two patients from two Chinese families who showed elevated Hb A levels but did not show any signs of β-thal. The variants were analyzed using direct sequencing of and prediction analysis. Moreover, the family's genetic history was investigated. We examined two probands from different Chinese families with elevated Hb A levels who were not afflicted with β-thal, although several nucleotide changes were found at codon 81 (CT>CT) (: c.246C>A) in Family 1 and a compound heterozygosity for codon 40 (AG>AG) (: c.122G>A) and IVS-II-478 (C>A) (: c.316-373C>A) in Family 2. After investigating the genetic history of both families including the β-thal aspect, we found that these mutations were not responsible for the elevated Hb A levels. It is rarely reported that high Hb A level is not indicative of β-thal. In contrast, low or normal Hb A level is always found with β-thal due to other molecular defects that mask their β-thal genotype. Our results highlight the importance of considering the genetic factors related and unrelated to β-thal to improve the accuracy of future genetic counseling.