Identification of a variation in the IVSII of α2 gene and its frequency in the population of Guangxi

• The HBA2: c.301-24delGinsCTCGGCCC was detected in the populations of Guangxi.
• A qPCR system was designed for the HBA2: c.301-24delGinsCTCGGCCC frequency study.
• The allele frequency of HBA2: c.301-24delGinsCTCGGCCC in Guangxi was 0.184%.
• The HBA2:c.301-24delGinsCTCGGCCC carrier would indicate an abnormality in MLPA.

ObjectiveDuring thalassemia screening, a previously unidentified α2 gene variation in α-globin gene cluster was isolated. This variation was distinct from other variations known to confer thalassemia as assessed by conventional thalassemia genotype analysis. Because the sample in the thalassemia screening was positive (MCV = 83.6 fL, MCH = 26.1 pg/cell, Hb = 11.3 g/dL), further analysis was required.Material and methodsMLPA (multiplex ligation-dependent probe amplification) and sequencing were used for analysis, and a qPCR system was designed for the frequency study.ResultsThe MLPA result showed that there was a mutation or small fragment deletions between 34247 (160 bp probe) and 34618 (196 bp probe) in α-globin gene cluster (NG_000006.1). Through sequencing, this variation was identified as HBA2: c.301-24delGinsCTCGGCCC. The gene polymorphisms similar to HBA2:c.301-24delGinsCTCGGCCC are α121 and α212. Since α212 is unrelated to microcytosis, and the structure of HBA2: c.301-24delGinsCTCGGCCC is similar to α212, this change is more appropriately considered as a polymorphism. The allele frequency of HBA2: c.301-24delGinsCTCGGCCC is 0.184% in this region.ConclusionsThere is a certain ratio for HBA2:c.301-24delGinsCTCGGCCC carriers among the Chinese population. The HBA2:c.301-24delGinsCTCGGCCC variant results in an abnormal result from MLPA analysis. Investigators performing thalassemia screening in Guangxi region should be aware of the HBA2:c.301-24delGinsCTCGGCCC variant to avoid misinterpretation of the MLPA results.