AUTHOR=Zhong Liangying , Wang Ye , Lin Wenbin , Yao Zhenrong , Zhang Jiang , Xu Hongxu , Feng Pinning , Xu Lijuan 

TITLE=Prenatal Genetic Counseling in a Chinese Pregnant Woman With Rare Thalassemia: A Case Report

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.670168

DOI=10.3389/fgene.2021.670168

ISSN=1664-8021

ABSTRACT=Background: Prenatal genetic counseling can be difficult, especially when it is related to fetuses with a rare thalassemia. Intronic variant located far from obvious regulatory sequences in the HBB gene could be very difficult to evaluate whether 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.316-45 G>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 gestation. Red blood cell counts, high performance liquid chromatography (HPLC) was consistent with the clinical manifestations of anemia. Multiplex gap-polymerase chain (gap-PCR) displayed the 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.316-45 G>C)] that has not been previously reported in the HbVar database. Thus, a rare combination of α+-thal and a compound heterozygosity of HbJ-Bangkokand [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 analysis. 
Conclusion: This study enlarges the mutation spectrum of beta-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.