Frontiers in Genetics (Mar 2023)

Case report: Long-read sequencing identified a novel 14.9-kb deletion of the α-globin gene locus in a family with α-thalassemia in China

  • Yan Yuan,
  • Xia Zhou,
  • Jing Deng,
  • Qun Zhu,
  • Zanping Peng,
  • Liya Chen,
  • Ya Zou,
  • Aiping Mao,
  • Wanli Meng,
  • Minhui Ma,
  • Hongliang Wu

DOI
https://doi.org/10.3389/fgene.2023.1156071
Journal volume & issue
Vol. 14

Abstract

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Background: Thalassemia is a hereditary blood disease resulting from globin chain synthesis impairment because of α- and/or β-globin gene variants. α-thalassemia is characterized by non-deletional and deletional variants in the HBA gene locus, of which rare deletional variants are difficult to detect by conventional polymerase chain reaction (PCR)-based methods.Case report: We report the case of a one-month-old boy, who and his mother had abnormal hematological parameters, while his father had normal hematology. Conventional PCR-reverse dot blot (RDB) was performed for all family members to analyze the 23 most common thalassemia variants in China, but did not identify any pathologic variants. Single-molecule real-time (SMRT) long-read sequencing (LRS) technology was then performed and identified an unreported 14.9-kb large deletion (hg38 chr16:168,803-183,737) of the α-globin gene locus, which disrupted both HBA1 and HBA2 genes in the proband and his mother. The exact breakpoints of the deletion were confirmed by gap-PCR and Sanger sequencing.Conclusion: We have detected a novel large deletion in α-globin gene locus in China, which not only enriches the variant spectrum of thalassemia, but also demonstrates the accuracy and efficiency of LRS in detecting rare and novel deletions.

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