{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Singha K"],"funding":["Khon Kaen University","Health System Research Institute"],"pagination":["8872"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12469752"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(18)"],"pubmed_abstract":["Variants of uncertain significance (VUS) are often challenging for genetic counseling and require additional data for accurate variant classification. This study aims to describe the genotype-phenotype correlation of the seven β-globin gene variants found in Thailand. Retrospective data in a total of 45,914 subjects encountered at our diagnostic laboratory from January 2012 to December 2024 were reviewed. A total of 33 leftover EDTA blood specimens, suspected of having β-globin gene defects, were included. Eighty-nine normal subjects were also analyzed to confirm phenotypic expression of the variants. The whole β-globin and Krüppel-like factor 1 (KLF1) genes were examined using PCR-based methods. Seven nucleotide variants were identified among 33 suspected subjects, including a novel (β-206(C>G)), four hitherto undescribed in Thailand [β-198(A>G), βIVSII-180(T>C), βIVSII-337(A>G), and β*233(G>C)], and two known variants [β-50(G>A) and βIVSII-258(G>A)]. The β-198(A>G) and β*233(G>C) variants were also identified in 1.69% of normal subjects, indicating neutral DNA polymorphisms. All subjects of β-198(A>G), βIVSII-180(T>C), βIVSII-258(G>A), and βIVSII-337(A>G) with borderline Hb A2 levels had KLF1 mutations. Compound heterozygous β-206(C>G) and known β+-thalassemia trait revealed β-thalassemia trait phenotype. In silico pathogenicity prediction showed that the β-206(C>G), β-198(A>G), βIVSII-180(T>C), βIVSII-258(G>A), βIVSII-337(A>G), and β*233(G>C) were associated with benign variants. It was found that heterozygous β-50(G>A) had elevated Hb A2 levels resembling those of β-thalassemia trait. However, the association of the β-50(G>A) and Hb E or β-thalassemia revealed a phenotype of Hb E or β-thalassemia trait. Most prediction tools indicate that the β-50(G>A) is associated with benign variants; however, PromoterAI revealed that the β-50(G>A) is associated with under-expression of the β-globin gene with high sensitivity. Based on these findings, the β-50(G>A) is most likely a very mild β+-thalassemia allele. This study described the genotype-phenotype correlation of known and novel β-globin gene variants found in Thailand. The data should prove useful for accurate variant classification, genetic counseling, and a prevention and control program of severe thalassemia diseases in Thailand."],"journal":["International journal of molecular sciences"],"pubmed_title":["Genotype-Phenotype Correlation of Seven Known and Novel β-Globin Gene Variants."],"pmcid":["PMC12469752"],"funding_grant_id":["HSRI 68-049","RP-68 Research Center"],"pubmed_authors":["Fucharoen G","Singha K","Pansuwan A","Fucharoen S"],"additional_accession":[]},"is_claimable":false,"name":"Genotype-Phenotype Correlation of Seven Known and Novel β-Globin Gene Variants.","description":"Variants of uncertain significance (VUS) are often challenging for genetic counseling and require additional data for accurate variant classification. This study aims to describe the genotype-phenotype correlation of the seven β-globin gene variants found in Thailand. Retrospective data in a total of 45,914 subjects encountered at our diagnostic laboratory from January 2012 to December 2024 were reviewed. A total of 33 leftover EDTA blood specimens, suspected of having β-globin gene defects, were included. Eighty-nine normal subjects were also analyzed to confirm phenotypic expression of the variants. The whole β-globin and Krüppel-like factor 1 (KLF1) genes were examined using PCR-based methods. Seven nucleotide variants were identified among 33 suspected subjects, including a novel (β-206(C>G)), four hitherto undescribed in Thailand [β-198(A>G), βIVSII-180(T>C), βIVSII-337(A>G), and β*233(G>C)], and two known variants [β-50(G>A) and βIVSII-258(G>A)]. The β-198(A>G) and β*233(G>C) variants were also identified in 1.69% of normal subjects, indicating neutral DNA polymorphisms. All subjects of β-198(A>G), βIVSII-180(T>C), βIVSII-258(G>A), and βIVSII-337(A>G) with borderline Hb A2 levels had KLF1 mutations. Compound heterozygous β-206(C>G) and known β+-thalassemia trait revealed β-thalassemia trait phenotype. In silico pathogenicity prediction showed that the β-206(C>G), β-198(A>G), βIVSII-180(T>C), βIVSII-258(G>A), βIVSII-337(A>G), and β*233(G>C) were associated with benign variants. It was found that heterozygous β-50(G>A) had elevated Hb A2 levels resembling those of β-thalassemia trait. However, the association of the β-50(G>A) and Hb E or β-thalassemia revealed a phenotype of Hb E or β-thalassemia trait. Most prediction tools indicate that the β-50(G>A) is associated with benign variants; however, PromoterAI revealed that the β-50(G>A) is associated with under-expression of the β-globin gene with high sensitivity. Based on these findings, the β-50(G>A) is most likely a very mild β+-thalassemia allele. This study described the genotype-phenotype correlation of known and novel β-globin gene variants found in Thailand. The data should prove useful for accurate variant classification, genetic counseling, and a prevention and control program of severe thalassemia diseases in Thailand.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-02T03:17:54.837Z","creation":"2026-05-02T03:11:46Z"},"accession":"S-EPMC12469752","cross_references":{"pubmed":["41009440"],"doi":["10.3390/ijms26188872"]}}