Genotypes of thalassemia in children: an analysis of 30 417 cases.

Objectives To investigate the distribution of genotypes of thalassemia in children in Guangxi, China. Methods A total of 30 417 children with positive results of thalassemia screening in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2011 to December 2019 were enrolled. Single-tube multiplex PCR, agarose gel electrophoresis, and reverse dot blot hybridization technique were used for the detection of common α- and β-thalassemia genes. Gap-PCR or gene sequence analysis was performed for 2 703 children suspected of rare thalassemia. Results Among the 30 417 children with positive results of thalassemia screening, 23 214 (76.32%) were diagnosed with thalassemia, and the detection rates of α-thalassemia, β-thalassemia, and α-thalassemia with β-thalassemia were 47.77%, 23.75%, and 4.80% respectively. A total of 13 types of α-thalassemia alleles (18 480 alleles in total) were detected, mainly --SEA (54.98%), including seven rare alleles, i.e., --THAI (0.43%), HKαα (0.02%), -α30 (0.01%), -α1.0 (0.01%), -α2.4 (0.01%), -α21.9 (0.01%), and HBA2:C272-279 del (0.01%). A total of 17 types of β-thalassemia alleles (9 168 alleles in total) were detected, mainly CD41-42 (47.79%), followed by CD17 (25.53%), including three rare alleles, i.e., IVS-II-5 (0.02%), IVS-I-2 (0.01%), and Gγ(Aγδβ)0 (0.01%). A total of 37 genotypes were detected in 14 531 children with α-thalassemia, among which the most common 6 genotypes were --SEA/αα (52.20%), -α3.7/αα (13.24%), αCSα/αα (7.52%), -α4.2 (6.06%), --SEA/-α3.7 (5.91%), and αWSα/αα (3.41%), accounting for 88.34%. A total of 49 genotypes were detected in 7 223 children with β-thalassemia, among which the most common 6 genotypes were CD41-42/βN (45.81%), CD17/βN (24.30%), IVS-II-654/βN (7.49%), -28/βN (5.62%), CD71-72/βN (4.42%), and CD26/βN (3.94%), accounting for 91.13%. A total of 137 genotypes were detected in 1 460 children with both α- and β-thalassemia, mainly --SEA/αα combined with CD41-42/βN (14.17%) and CD17/βN (8.35%). A total of 2 050 children were diagnosed with hemoglobin H disease (α0/α+), among whom 134 had β-thalassemia heterozygote and 12 had Bart hydrops fetalis syndrome (--SEA/--SEA); 355 children were diagnosed with β-thalassemia double heterozygote, and 128 were diagnosed with β-thalassemia homozygote, including 93 children with α-thalassemia. Conclusions There are diverse gene mutations and rich genotypes of thalassemia among children in Guangxi, and α-thalassemia is more common, with --SEA/αα as the major genotype. There is a high proportion of children with both α- and β-thalassemia, and there are relatively high incidence rates of β-thalassemia double heterozygote and homozygote (intermedia and major).