Genotypic-phenotypic heterogeneity of δβ-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) in India.

Journal Article (Journal Article)

Large deletions in the β-globin gene cluster lead to increased HbF levels by delaying the γ- to β-globin switch process. However, these deletions when inherited as a homozygous condition or when co-inherited with β-thalassemia result in variable clinical phenotypes. Individuals or families with a clinically presenting child, where the parents had HbF levels ≥ 10%, were further screened for the presence of large β-globin cluster deletions. Six deletions in the β-globin gene cluster were screened by GAP-PCR, and the uncharacterized deletions were further analyzed by gene dosage or by multiplex ligation-dependent probe amplification (MLPA). Among 192 individuals suspected for the inheritance of large deletions, 138 were heterozygous for large deletions, 45 were compound heterozygous of a large β-globin cluster deletion and β-thalassemia, and 9 were found to be homozygous for deletions. Among the heterozygotes, the Asian Indian inversion-deletion was found to be the most common deletion (39.9%), followed by the HPFH-3 deletion (30.0%). Other deletions 49.3 kb, δβ-thalassemia (21.2%), and 32.6 kb deletion (4.4%) were also found to be prevalent in our population. Patients compound heterozygous or homozygous for HPFH-3 and 32.6 kb deletions showed a milder clinical presentation, as compared with the patients compound heterozygous or homozygous for the Asian Indian inversion-deletion and 49.3 kb δβ-thalassemia. This comprehensive study highlights the mutation spectrum of large β-globin cluster deletions and the clinical heterogeneity in the patients homozygous or compound heterozygous with β-thalassemia, thus asserting the need for molecular characterization of these deletions.

Full Text

Duke Authors

Cited Authors

  • Hariharan, P; Kishnani, P; Sawant, P; Gorivale, M; Mehta, P; Kargutkar, N; Colah, R; Nadkarni, A

Published Date

  • July 2020

Published In

Volume / Issue

  • 99 / 7

Start / End Page

  • 1475 - 1483

PubMed ID

  • 32524201

Electronic International Standard Serial Number (EISSN)

  • 1432-0584

Digital Object Identifier (DOI)

  • 10.1007/s00277-020-04081-8


  • eng

Conference Location

  • Germany