The pedigree analysis and prenatal diagnosis of Hong Kongαα Thalassemia and the sequence analysis of Hong Kongαα Allele

作者：Wenjuan Wang, Haiqing Zheng, Dan Zeng, Linbin Jiang, Donglan Yu, Yuzhong Yang, Feng Qiao, Yang Xia, Chunjiang Zhu · 发表于：Molecular Genetics & Genomic Medicine · 年份：2020 · DOI：10.1002/mgg3.1285 · 被引用次数：3 · 研究领域：Hemoglobinopathies and Related Disorders、Blood groups and transfusion、Complement system in diseases

Abstract Background Thalassemia is one of the most common monogenic hemolytic disorders in the world. Hong Kongαα ( HKαα ) thalassemia was initially found among the people of southern China. Because of the complexity of genetic changes in HKαα thalassemia, we lack a precise sequence analysis of the HKαα allele. Here we aim to detect the specific genotype and trace the law of inheritance of this rare genotype. Methods We recruited an unprecedented huge pedigree containing 11 individuals carrying the HKαα thalassemia gene and 4 nongenetic‐related patients suffering from HKαα from south China. Regular hematological analysis and routine genetic screening were performed on the pedigree and two‐round nested PCR (polymerase chain reaction) for HKαα thalassemia were performed on each individual. The first‐generation gene sequencing was performed on six individuals, including four nongenetic‐related patients. Result We found that five family members were positive for the HKαα allele. Patients Ⅱ‐2, Ⅲ‐1, and Ⅱ‐3 with only HKαα/‐‐ SEA or HKαα/‐α 4.2 presented with α‐thalassemia minor trait. Ⅰ‐1, the carrier of both HKαα/‐α 3.7 and β 41‐42 /β N , showed a typical β‐thalassemia trait. Fetus with genotype HKαα/‐α 4.2 alone was not likely to suffer from any deleterious effects after birth. The whole sequence of HKαα allele revealed that HKαα alleles in the six patients shared a high similarity, implying that all HKαα alleles are likely from the same ancestor. Moreover, pedigree and sequencin...