Characterization of a Novel 71.8 kb α0-Thalassemia Deletion and Subsequent Summary of a Practical Procedure for Thalassemia Molecular Diagnosis

Hemoglobin. 2020 Jul;44(4):259-263. doi: 10.1080/03630269.2020.1790385. Epub 2020 Jul 10.

Abstract

Thalassemia is the most common monogenic disorder around the world. Based on the principle of genotype-phenotype correlation, identification of thalassemia mutations is the essential prerequisite for clinical diagnosis and management. Because only common mutations are routinely detected, the identification of rare or undetermined mutations is a challenge for clinical laboratories. Herein, a proband presenting with inconsistent phenotype-genotype correlation after routine molecular screening was investigated by multiplex ligation-dependent probe amplification (MLPA), targeted-next generation sequencing (targeted-NGS), gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. Eventually, a novel 71.8 kb deletion (- -71.8) was identified and characterized, which included HBZ (ζ), HBA2 (α2), and HBA1 (α1) genes and was causing α0-thalassemia (α0-thal). Furthermore, we summarized a practical procedure based on accumulated experience in studies and clinical practice, which can be a guide for molecular screening and clinical diagnosis of thalassemia, especially for identification of undetermined or novel mutations.

Keywords: Genotyping; novel deletion; practical procedure; targeted next-generation sequencing (targeted-NGS); thalassemia.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • China
  • Erythrocyte Indices
  • Female
  • Genetic Association Studies
  • Genetic Testing* / methods
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Molecular Diagnostic Techniques
  • Pedigree
  • Phenotype
  • Sequence Analysis, DNA
  • Sequence Deletion*
  • alpha-Globins / genetics*
  • alpha-Thalassemia / blood
  • alpha-Thalassemia / diagnosis*
  • alpha-Thalassemia / genetics*

Substances

  • alpha-Globins