title: Sickle cell disease resulting from uniparental disomy in a child who inherited sickle cell trait.
abstract: Sickle cell disease (SCD) is a classic example of a disorder with recessive Mendelian inheritance, in which each parent contributes one mutant allele to an affected offspring. However, there are exceptions to that rule. We describe here the first reported case of conversion of inherited sickle cell trait to SCD by uniparental disomy (UPD) resulting in mosaicism for SS and AS erythrocytes. A 14-year-old boy presented with splenomegaly and hemolysis. Although his father has sickle cell trait, his mother has no abnormal hemoglobin (Hb). DNA sequencing, performed to rule out Hb S/β-thalassemia, detected homozygous Hb SS. Further studies revealed mosaic UPD of the β-globin locus, more SS erythroid progenitors than AS, but a reverse ratio of erythrocytes resulting from the survival advantage of AS erythrocytes. This report exemplifies non-Mendelian genetics wherein a patient who inherited sickle cell trait has mild SCD resulting from postzygotic mitotic recombination leading to UPD.
authors.affiliation: Division of Pathology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Swensen
authors.forename: Archana M
authors.initials: AM
authors.lastname: Agarwal
authors.forename: Jose M
authors.initials: JM
authors.lastname: Esquilin
authors.forename: Sabina
authors.initials: S
authors.lastname: Swierczek
authors.forename: Ajay
authors.initials: A
authors.lastname: Perumbeti
authors.forename: Dottie
authors.initials: D
authors.lastname: Hussey
authors.forename: Margaret
authors.initials: M
authors.lastname: Lee
authors.forename: Clinton H
authors.initials: CH
authors.lastname: Joiner
authors.forename: Genevieve
authors.initials: G
authors.lastname: Pont-Kingdon
authors.forename: Elaine
authors.initials: E
authors.lastname: Lyon
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000378:metabolism; D005260:Female; D006441:Hemoglobin A / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008938:Mitosis / Q000235:genetics; D009030:Mosaicism; D017354:Point Mutation; D012805:Sickle Cell Trait / Q000097:blood / Q000235:genetics*; D024182:Uniparental Disomy; D055544:beta-Globins / Q000235:genetics
chemical_list: D006451:Hemoglobin, Sickle; D055544:beta-Globins; D006441:Hemoglobin A