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Background <p>Zeta (ζ)-thalassemia is a rare form of thalassemia. In clinical practice, ζ-thalassemia is frequently a missed diagnosis due to its normal hematological phenotype. Here, we report a novel <i>HBZ</i>-<i>HBZP1</i> deletion within the α-globin gene cluster.</p> Methods <p>The proband was first tested for six common deletional α-thalassemia using Gap-PCR and for three point mutations using PCR-based reverse dot blot (PCR-RDB). Multiplex ligation-dependent probe amplification (MLPA) was subsequently employed to detect copy number variations in the α-globin gene cluster. Third-generation sequencing (TGS) was performed to characterize potential deletion locations. Finally, based on the breakpoints suggested by TGS, Gap-PCR with specific primers followed by Sanger sequencing confirmed the precise breakpoints.</p> Results <p>The proband’s hematological parameters were normal, except for a decreased Hb A<sub>2</sub> level (2.3%). Gap-PCR showed an internal control band but no normal control band. MLPA indicated a copy number of zero for probes 292 and 391 and a copy number of two for probe 190, suggesting concomitant deletion and duplication events. TGS identified a 10.7&#xa0;kb deletion (Chr16:154,355 − 165,114del; NG_000006.1:g.15218_25972del) and a homozygous point mutation (Chr16:169,854T &gt; C; NG_000006.1:g.30717T &gt; C; rs2258435). Subsequent Sanger sequencing of the Gap-PCR product amplified with specific primers validated both the deletion breakpoints (NG_000006.1:g.15218_25972del) and the point mutation (NG_000006.1:g.30717T &gt; C), which was consistent with the TGS findings.</p> Conclusion <p>This study describes the identification of a novel 10.7&#xa0;kb deletion (Nanning deletion, -ζ<sup>10.7 kb</sup>) causing ζ-thalassemia. Our findings confirm that this deletion is associated with a silent carrier phenotype.</p>

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Identification of a novel 10.7 kb deletion (Nanning deletion; -ζ10.7 kb) in a Chinese female

  • 期刊论文

  • 发表日期：

    2025年10月23日

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  • Youqiong Li,
  • Lihong Zheng,
  • Liang Liang,
  • Yu Zheng,
  • Jinping Bai

摘要

Background

Zeta (ζ)-thalassemia is a rare form of thalassemia. In clinical practice, ζ-thalassemia is frequently a missed diagnosis due to its normal hematological phenotype. Here, we report a novel HBZ-HBZP1 deletion within the α-globin gene cluster.

Methods

The proband was first tested for six common deletional α-thalassemia using Gap-PCR and for three point mutations using PCR-based reverse dot blot (PCR-RDB). Multiplex ligation-dependent probe amplification (MLPA) was subsequently employed to detect copy number variations in the α-globin gene cluster. Third-generation sequencing (TGS) was performed to characterize potential deletion locations. Finally, based on the breakpoints suggested by TGS, Gap-PCR with specific primers followed by Sanger sequencing confirmed the precise breakpoints.

Results

The proband’s hematological parameters were normal, except for a decreased Hb A2 level (2.3%). Gap-PCR showed an internal control band but no normal control band. MLPA indicated a copy number of zero for probes 292 and 391 and a copy number of two for probe 190, suggesting concomitant deletion and duplication events. TGS identified a 10.7 kb deletion (Chr16:154,355 − 165,114del; NG_000006.1:g.15218_25972del) and a homozygous point mutation (Chr16:169,854T > C; NG_000006.1:g.30717T > C; rs2258435). Subsequent Sanger sequencing of the Gap-PCR product amplified with specific primers validated both the deletion breakpoints (NG_000006.1:g.15218_25972del) and the point mutation (NG_000006.1:g.30717T > C), which was consistent with the TGS findings.

Conclusion

This study describes the identification of a novel 10.7 kb deletion (Nanning deletion, -ζ10.7 kb) causing ζ-thalassemia. Our findings confirm that this deletion is associated with a silent carrier phenotype.