title: A late onset sickle cell disease reveals a mosaic segmental uniparental isodisomy of chromosome 11p15.
abstract: We report, in a 78-year old man constitutionally heterozygous for the sickle cell trait, a late onset sickle cell disease (SCD) caused by a mosaic segmental uniparental isodisomy of chromosome 11p15. The mosaic loss of heterozygosity (LOH) of the HBB gene was suggested in front of an unusually weak β(A) peak at Sanger direct sequencing and a semi-quantitative FRET Light Cycler method which showed a low expression of the β(A) allele compared to the β(S) allele. A SNP array analysis then revealed a 45.9 Mb LOH on almost the whole short arm of chromosome 11 without any copy loss number and with an estimated level of mosaicism of 80%. Culture and genotyping of erythroblastic burst forming units confirmed the presence of AS and SS hematopoietic cells in the proportions of 2/3 and 1/3, respectively. Such a late-onset SCD had already been described but for a much younger patient (a 14-year-old boy). This discrepancy could be explained either by a much lower degree of mosaicism at birth in our proband (and thus a much more delayed clinical expression) or by inter-individual variations (modifier genes for example) that could have slowed down the positive selection of S/S clones.
authors.affiliation: Laboratoire CERBA, 95066 Cergy-Pontoise cedex 9, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vinatier
authors.affiliation: Service de médecine polyvalente, Centre hospitalier Antoine Gayraud, 11890 Carcassonne cedex 9, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Martin
authors.affiliation: Laboratoire CERBA, 95066 Cergy-Pontoise cedex 9, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Costa
authors.affiliation: Laboratoire CERBA, 95066 Cergy-Pontoise cedex 9, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bazin
authors.affiliation: Service d'hématologie biologique, GH Henri-Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Giraudier
authors.affiliation: Unité de Pathologie Moléculaire du Globule Rouge, Laboratoire de Biochimie et Biologie moléculaire, Hôpital Edouard Herriot, Hospices Civils de Lyon & Université Claude Bernard-Lyon 1, Lyon, France. Electronic address: philippe.joly@chu-lyon.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
mesh_terms: D000368:Aged; D000755:Anemia, Sickle Cell / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009030:Mosaicism; D024182:Uniparental Disomy / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal
keywords: 11p15 isoparental isodisomy; Late-onset SCD; Loss of heterozygosity; Mosaicism