METHODS: During 2012 to 2017, suspected thalassemia people were detected for common α- and β-thalassemia mutations by gap-Polymerase Chain Reaction (PCR) and reverse dot blot (RDB) analysis in Peking Union Medical College Hospital. One thousand and fifty-nine people with thalassemia mutations were analyzed retrospectively. We picked mutated individuals who originally came from northern areas, and conducted telephone follow-up survey in order to collect their ancestral information. Besides, we used "thalassemia", "mutation", and "Southeast Asian countries" as keywords to search the relevant studies in PubMed and Embase databases.
RESULTS: All carriers included in our study were resided in northern China. Among them, 17.3% were native northerners and 82.7% were immigrants from southern China. Although substantial difference was found in α- and β-thalassemia ratio and detailed spectrum of α- and β-globin mutation spectrum between our data and data obtained from a previous meta-analysis literature focused on southern China, the most common gene mutations were the same. Similar β-thalassemia mutation spectrum was found among Thai, Malaysian Chinese, and Guangdong people, however, no other similarities in gene profile were found between Chinese and other ethnic groups in Southeast Asia.
CONCLUSION: Chinese people in different areas had similar gene mutation, whereas they had significantly different mutation spectrums from other ethnic groups in Southeast Asia.
MAIN BODY: Clinical manifestations of non-deletional in alpha thalassaemia are varied and have more severe phenotype compared to deletional forms of alpha thalassaemia. Literature for the molecular mechanisms of common non-deletional alpha thalassaemia including therapeutic measures that are necessarily needed for the understanding of these disorders is still in demand. This manuscript would contribute to the better knowledge of how defective production of the α-globin chains due to mutations on the alpha-globin genes and/or the regulatory elements leads to alpha thalassaemia syndrome.
CONCLUSION: Since many molecular markers are associated with the globin gene expression and switching over during the developmental stages, there is a need for increased awareness, new-born and prenatal screening program, especially for countries with high migration impact, and for improving the monitoring of patients with α-thalassaemia.
METHODS: The most used methods for the quantification of Hb A2 are based on automated high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). In particular Hb analyses were performed by HPLC on three dedicated devices. DNA analyses were performed according to local standard protocols.
RESULTS: Here, we described eight new δ-globin gene variants discovered and characterized in some laboratories in Northern Italy in recent years. These new variants were added to the many already known Hb A2 variants that were found with an estimated frequency of about 1-2% during the screening tests in our laboratories.
CONCLUSIONS: The knowledge recognition of the delta variant on Hb analysis and accurate molecular characterization is crucial to provide an accurate definitive thalassemia diagnosis, particularly in young subjects who would like to ask for a prenatal diagnosis or preimplantation genetic diagnosis.
SETTING: Haematology Lab, Department of Biomedical Science, University of Malaya.
PARTICIPANTS: Eight couples characterised as β-thalassaemia carriers where both partners posed the same β-globin gene mutations at CD41/42, IVS1-5 and IVS2-654, were recruited in this study.
OUTCOME MEASURES: Genotyping was performed by allele specific-PCR and the locations of SNPs were identified after sequencing alignment.
RESULTS: Genotype analysis revealed that at least one paternal SNP was present for each of the couples. Amplification on free-circulating DNA revealed that the paternal mutant allele of SNP was present in three fcDNA. Thus, the fetuses may be β-thalassaemia carriers or β-thalassaemia major. Paternal wild-type alleles of SNP were present in the remaining five fcDNA samples, thus indicating that the fetal genotypes would not be homozygous mutants.
CONCLUSIONS: This preliminary research demonstrates that paternal allele of SNP can be used as a non-invasive prenatal diagnosis approach for at-risk couples to determine the β-thalassaemia status of the fetus.