Thalassemia genetic screening of pregnant women with anemia in Northern China through comprehensive analysis of thalassemia alleles (CATSA)

Abstract

Thalassemia is an inherited blood disorder and traditionally considered more prevalent in Southern China. However, with increased migration and intermarriage, more and more thalassemia carriers had been reported in Northern China. The lack of screening for thalassemia carriers may also result in missed diagnosis in Northern China. Additionally, thalassemia carriers are usually asymptomatic or mild anemia, but their anemia can get worse during pregnancy. Iron deficiency anemia (IDA) is also one of the causes of anemia during pregnancy. In particular, both IDA and thalassemia are characterized by microcytic hypochromic anemia. The overlap of symptoms and the presence of thalassemia carriers with IDA may lead to misdiagnosis. In this study, long-read sequencing based approach termed comprehensive analysis of thalassemia alleles (CATSA) had been performed for 244 pregnant women in Northern China whose results of routine blood examinations were abnormal. As a result, 16.39 % (40/244) of the anemic pregnant women carried at least one mutation of thalassemia. One Hb H patient and a rare α-globin gene triplication combined with β-thalassemia were also identified. Of the 44 thalassemia variants detected, the −α^3.7, −^SEA and HBB:c.316-197C > T were the most common variants. CATSA is of great significance for determining exact genotype of 22.50 % (9/40) thalassemia carriers because 8 variants they carried were outside the detection range of routine genetic tests. It is noted that 2 novel deletions of HBA gene were identified, expanding the genotype spectrum of α-thalassemia. Our findings demonstrate the importance of thalassemia screening in Northern China. Future research should focus on expanding screening to include more diverse populations.