Human Genetics

, Volume 102, Issue 6, pp 629–634

The Cretan type of non-deletional hereditary persistence of fetal hemoglobin [Aγ–158C→T] results from two independent gene conversion events

  • G. P. Patrinos
  • Panagoula Kollia
  • Aphrodite Loutradi-Anagnostou
  • Dimitris Loukopoulos
  • Manoussos N. Papadakis
Original investigation

DOI: 10.1007/s004390050753

Cite this article as:
Patrinos, G., Kollia, P., Loutradi-Anagnostou, A. et al. Hum Genet (1998) 102: 629. doi:10.1007/s004390050753

Abstract

We report a new type of non-deletional hereditary persistence of fetal hemoglobin that is due to a C→T transition at position –158, relative to the Cap site of the human Aγ-globin gene. This mutation was identified in three unrelated adult cases presenting slightly elevated levels of fetal hemoglobin (Hb F), i.e. 2.9–5.1%, and normal hematological indices. Our sequencing results, from both polymerase chain reaction-amplified and subcloned DNA fragments, indicate that the Aγ–158C→T mutation occurred by two independent gene conversion events in the three cases studied. In addition, hematological and molecular data, including restriction fragment length polymorphism haplotyping in the β-globin gene cluster, extended haplotype analysis inside the γ-globin gene region and routine analysis of three tandem repeat loci (D1S80, 3′-HVR/apoB and F8vWf), led us to conclude that the Aγ–158C→T mutation in one of the three cases occurred recently in the parental germ line (P=99.47%), representing the first example of a de novo gene conversion event identified in humans.

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • G. P. Patrinos
    • 1
  • Panagoula Kollia
    • 2
  • Aphrodite Loutradi-Anagnostou
    • 1
  • Dimitris Loukopoulos
    • 2
  • Manoussos N. Papadakis
    • 1
  1. 1.Laikon General Hospital, Center for Thalassemia, Unit of Prenatal Diagnosis, Athens, GreeceGreece
  2. 2.University of Athens, School of Medicine, First Department of Internal Medicine, Athens, GreeceGreece