Original investigation

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. PatrinosAffiliated withLaikon General Hospital, Center for Thalassemia, Unit of Prenatal Diagnosis, Athens, Greece
  • , Panagoula KolliaAffiliated withUniversity of Athens, School of Medicine, First Department of Internal Medicine, Athens, Greece
  • , Aphrodite Loutradi-AnagnostouAffiliated withLaikon General Hospital, Center for Thalassemia, Unit of Prenatal Diagnosis, Athens, Greece
  • , Dimitris LoukopoulosAffiliated withUniversity of Athens, School of Medicine, First Department of Internal Medicine, Athens, Greece
  • , Manoussos N. PapadakisAffiliated withLaikon General Hospital, Center for Thalassemia, Unit of Prenatal Diagnosis, Athens, Greece

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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.