The Cretan type of non-deletional hereditary persistence of fetal hemoglobin [A gamma-158C-->T] results from two independent gene conversion events.
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 Agamma-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 A gamma -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 beta-globin gene cluster, extended haplotype analysis inside the gamma-globin gene region and routine analysis of three tandem repeat loci (D1S80, 3'HVR/apoB and F8vWf), led us to conclude that the A gamma -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.
Patrinos
G P
GP
Laikon General Hospital, Center for Thalassemia, Unit of Prenatal Diagnosis, Athens, Greece.
Kollia
P
P
Loutradi-Anagnostou
A
A
Loukopoulos
D
D
Papadakis
M N
MN
D005319:Fetal Hemoglobin / Q000235:genetics*; D005785:Gene Conversion; D005914:Globins / Q000235:genetics*; D006115:Greece; D006801:Humans; D017354:Point Mutation; D012315:RNA Caps / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid
D012315:RNA Caps; D005914:Globins; D005319:Fetal Hemoglobin