Identification of a novel 91.5 kb-deletion (αα) FJ in the α-globin gene cluster using single-molecule real-time (SMRT) sequencing

• Published in: The journal of maternal-fetal & neonatal medicine 2023-12, Vol.36 (2), p.2254890-2254890
• Main Authors: Xu, Liangpu, Chen, Meihuan, Zheng, Junhao, Zhang, Siwen, Zhang, Min, Chen, Lingji, He, Qianqian, Guo, Danhua, Lin, Na, Huang, Hailong
• Format: Article
• Language: English
• ISSN: 1476-7058; 1476-4954
• DOI: 10.1080/14767058.2023.2254890

OBJECTIVESTo present a novel 91.5-kb deletion of the α-globin gene cluster (αα)FJ identified by genetic assay and prenatal diagnosis in a Chinese family. SUBJECTS AND METHODSThe proband was a 34-year-old G3P1 (Gravida 3, Para 1) female at the gestational age of 21+ weeks with a history of an edematous fetus. A routine genetic assay (reverse dot blot hybridization, RDB) was performed to detect common thalassemia mutations. Multiplex ligation-dependent probe amplification (MLPA) and single-molecule real-time technology (SMRT) were used to detect rare thalassemia mutations. RESULTSThe hematological phenotypes of the proband, her mother, elder sister, husband, daughter, and nephew were consistent with the phenotype of α-thalassemia trait. No mutations were found in these family members by RDB, except for the proband's husband who carried an α-globin gene deletion --SEA/αα. MLPA results showed that the proband and other α-thalassemia-suspected relatives had heterozygous deletions around the POLR3K-3-463nt, HS40-178nt, and HBA-HS40-382nt probes. The 5'-breakpoint was out of probe scope and could not be determined. SMRT was performed and a 91.5-kb deletion (NC_000016.10: g.39268_130758del) in the α-globin gene cluster (αα)FJ was identified in the proband and other suspected relatives, which could explain their phenotypes. At the proband's gestational age of 22+ weeks, an amniotic fluid sample was collected and analyzed. As only the 91.5-kb deletion (αα)FJ was identified in the fetus with RDB, MLPA, and SMRT. The proband was suggested to continue the pregnancy. CONCLUSIONWe first reported a 91.5-kb deletion (NC_000016.10: g.hg38-chr16:39268-_130758del) of the HS-40 region in the α-globin gene cluster (αα)FJ identified in a Chinese family. Since the HS-40 loss of heterozygosity in combination with the heterozygous deletion --SEA might result in Hb Bart's hydrops fetalis, routine genetic assay, and SMRT were recommended to individuals at risk for prenatal diagnosis.