Molecular prevalence of HBB-associated hemoglobinopathy among reproductive-age adults and the prenatal diagnosis in Jiangxi Province, southern central China

Abstract

Background and aims: Hemoglobinopathy associated with the HBB gene, with its two general subtypes as thalassemia and abnormal hemoglobin (Hb) variants, is one of the most prevalent hereditary Hb disorders worldwide. Herein we aimed to elucidate the prevalence of ß-thalassemia and abnormal hemoglobin variants and the prenatal diagnosis of the HBB gene in Jiangxi Province, southern central China.Methods: Hematological indices and capillary Hb electrophoresis were conducted for 136,149 subjects who were admitted to Jiangxi Maternal and Child Health Hospital and requested for hemoglobinopathy investigation. Routine α- and ß-globin genotyping were performed by gap-polymerase chain reaction (Gap-PCR) and reverse dot-blot (RDB) hybridization for the 11,549 individuals suspected to be thalassemia carriers. For participants whose genotypes could not explain their hematological indices, further Sanger sequencing and Gap-PCR were conducted for the detection of rare or novel variants in related globin genes. Prenatal diagnosis was performed for 77 pregnant couples both carrying ß-thalassemia trait at appropriate gestational ages.Results: Among the 11,549 subjects, 2,548 individuals were identified with HBB-associated hemoglobinopathy based on molecular analysis. A total of 2,358 subjects were identified as ß-thalassemia heterozygous carriers and nine cases were diagnosed as compound heterozygous ß-thalassemia. Additionally, 125 cases were detected with composite α- and ß-thalassemia and the remaining 56 individuals with abnormal Hb variants in the HBB. A total of 35 types of variants were identified in the HBB gene, including 26 types of ß-thalassemia and nine types of abnormal Hb variants. Four novel variants were firstly reported, including one variant in HBA2 and three variants in HBB. Overall, 77 prenatal samples underwent ß-thalassemia molecular diagnosis; 20 fetuses were identified with normal ß-thalassemia genotypes, 30 fetuses as ß-thalassemia heterozygotes, 11 as homozygotes, and 16 as compound heterozygotes in HBB.Conclusion: We have demonstrated a relatively high prevalence rate at 1.872% of ß-hemoglobinopathies including common and rare ß-thalassemia as well as abnormal Hb variants among large child-bearing population in the Jiangxi area of southern central China for the first time. Our data presents that prenatal diagnosis is an effective way to prevent and control birth defects of ß-thalassemia.

Molecular characterization of similar Hb Lepore Boston-Washington in four Chinese families using third generation sequencing

“…Quanzhou region of Fujian province, located in Southeast China, displays a high prevalence of thalassemia, with a diversity and complexity of thalassemia 21 – 23 . Common α- and β-thalassemia gene variants in China are typically diagnosed by PCR-RDB and gap-PCR 12 , but they have limitations in the diagnosis of rare thalassemia variants. Third-generation sequencing technology has significant advantages in the diagnosis of thalassemia, and can detect almost all known globin gene variants 13 , 14 .…”

“…Common α- and β-thalassemia gene variants in China are typically diagnosed by PCR-reverse dot blot hybridization (PCR-RDB) and gap-PCR 12 . However, traditional diagnostic tools may lead to misdiagnosis of rare thalassemia genotypes.…”

Optimalisasi Kondisi PCR Untuk Amplifikasi Sekuen Gen HBB

“…Sebagai molekul protein yang berperan penting dalam pengangkutan oksigen, kekurangan atau bahkan tidak disintesisnya salah satu rantai globin berdampak pada kegagalan fungsi hemoglobin. Dalam 2 dekade terakhir telah banyak dilaporkan kasus kelainan genetik terkait hemoglobin di seluruh dunia termasuk Indonesia, diantaranya thalassemia dan hemoglobinopati (varian hemoglobin) (Luo et al, 2022;Modell & Darlison, 2008;Tangvarasittichai, 2011;Weatherall & Clegg, 2001;Wulandari, 2016).…”

Assessing the efficacy of hemoglobin electrophoresis as a diagnostic tool in moderate to severe anemia: a study protocol

“…Our work may serve as a foundation for genetic counselling, public awareness campaigns, and as a guide to enhance ß-thal prevention. 20 ME Fields et al(2022) did a study to concluded that children with non-SCAs had higher OEF than unaffected children, indicating that anaemia is the main cause of this compensatory mechanism. However, even adjusting for the effect of anaemia, children with SCA have considerably higher OEF than kids without SCAs, indicating that there are other pathophysiologic mechanisms in SCA than anaemia that affect cerebral metabolic demand.…”