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

Publication ,  Journal Article
Hariharan, P; Kishnani, P; Sawant, P; Gorivale, M; Mehta, P; Kargutkar, N; Colah, R; Nadkarni, A
Published in: Ann Hematol
July 2020

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.

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Published In

Ann Hematol

DOI

EISSN

1432-0584

Publication Date

July 2020

Volume

99

Issue

7

Start / End Page

1475 / 1483

Location

Germany

Related Subject Headings

  • delta-Thalassemia
  • beta-Thalassemia
  • Male
  • Inheritance Patterns
  • Infant
  • India
  • Immunology
  • Humans
  • Genetic Heterogeneity
  • Genetic Association Studies
 

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Hariharan, P., Kishnani, P., Sawant, P., Gorivale, M., Mehta, P., Kargutkar, N., … Nadkarni, A. (2020). Genotypic-phenotypic heterogeneity of δβ-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) in India. Ann Hematol, 99(7), 1475–1483. https://doi.org/10.1007/s00277-020-04081-8
Hariharan, Priya, Pooja Kishnani, Pratibha Sawant, Manju Gorivale, Pallavi Mehta, Neha Kargutkar, Roshan Colah, and Anita Nadkarni. “Genotypic-phenotypic heterogeneity of δβ-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) in India.Ann Hematol 99, no. 7 (July 2020): 1475–83. https://doi.org/10.1007/s00277-020-04081-8.
Hariharan P, Kishnani P, Sawant P, Gorivale M, Mehta P, Kargutkar N, et al. Genotypic-phenotypic heterogeneity of δβ-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) in India. Ann Hematol. 2020 Jul;99(7):1475–83.
Hariharan, Priya, et al. “Genotypic-phenotypic heterogeneity of δβ-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) in India.Ann Hematol, vol. 99, no. 7, July 2020, pp. 1475–83. Pubmed, doi:10.1007/s00277-020-04081-8.
Hariharan P, Kishnani P, Sawant P, Gorivale M, Mehta P, Kargutkar N, Colah R, Nadkarni A. Genotypic-phenotypic heterogeneity of δβ-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) in India. Ann Hematol. 2020 Jul;99(7):1475–1483.
Journal cover image

Published In

Ann Hematol

DOI

EISSN

1432-0584

Publication Date

July 2020

Volume

99

Issue

7

Start / End Page

1475 / 1483

Location

Germany

Related Subject Headings

  • delta-Thalassemia
  • beta-Thalassemia
  • Male
  • Inheritance Patterns
  • Infant
  • India
  • Immunology
  • Humans
  • Genetic Heterogeneity
  • Genetic Association Studies