Abstract
Background: Prenatal genetic counseling can be difficult, especially when it is related to fetuses with a rare thalassemia. An intronic variant located far from obvious regulatory sequences in the HBB gene could be very difficult to evaluate as it may affect the mRNA processing or cause β-thalassemia (β-thal). In the present study, a Chinese pregnant woman with HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] in combination with α+-thalassemia was reported, which can assist in prenatal genetic counseling.Case Report: A 26-year-old pregnant woman presented at the obstetric clinic for a routine pregnancy check at 12 weeks of gestation. Red blood counts and high-performance liquid chromatography (HPLC) were consistent with clinical manifestations of anemia. Multiplex gap-polymerase chain (gap-PCR) displayed rightward deletion (–α3.7/αα). Direct DNA sequencing of the δ-globin gene showed no mutation. Sanger sequencing of the β-globin gene showed a previously undescribed condition of double heterozygosity for HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] that has not been previously reported in the HbVar database. Thus, a rare combination of α+-thal and a compound heterozygosity of HbJ-Bangkok and [IVS-II-806(G>C)] with α+-thal (–α3.7/αα) was finally diagnosed. Prenatal genetic counseling was made based on the genotype and phenotype analyses.Conclusion: This study enlarges the mutation spectrum of β-globin gene and emphasizes DNA analysis in resolving unusual patterns in Hb analysis and the importance of sharing the observed rare undefined mutations and the possible interactions with known molecular defects, which can assist in prenatal genetic counseling.
Highlights
Beta-thalassemia characterized by insufficient or missing synthesis of the β-globin chain of hemoglobin is an autosomal recessive disorder (Origa, 2017)
We report a β-thalassemia patient with a normal level of HbA2 who had a point mutation in the intron 2 region of the β-globin gene [IVS-II-806(G>C), NM_000518.4, HBB: c.31645G>C] combined with HbJ-Bangkok associated with the α+thal (–α3.7/αα) mutation
A previously undescribed condition of double heterozygosity for HbJ-Bangkok and a deep intronic variant in the second intron of the β-globin gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] change at 806, a G>C mutation, and a potential 5′ splice site within the IVS-II was found. This deep intronic variant had not been previously reported in the HbVar database but reported with clinical significance “benign” in dbSNP Short Genetic Variation
Summary
Prenatal genetic counseling can be difficult, especially when it is related to fetuses with a rare thalassemia. An intronic variant located far from obvious regulatory sequences in the HBB gene could be very difficult to evaluate as it may affect the mRNA processing or cause β-thalassemia (β-thal). A Chinese pregnant woman with HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] in combination with α+-thalassemia was reported, which can assist in prenatal genetic counseling. Sanger sequencing of the β-globin gene showed a previously undescribed condition of double heterozygosity for HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] that has not been previously reported in the HbVar database. Prenatal genetic counseling was made based on the genotype and phenotype analyses
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