A late onset sickle cell disease reveals a mosaic segmental uniparental isodisomy of chromosome 11p15

作者：Vinatier Isabelle; Martin Xavier; Costa Jean Marc; Bazin Anne; Giraudier Stephane; Joly Philippe^*

来源：Blood Cells, Molecules, and Diseases, 2015, 54(1): 53-55.

DOI：10.1016/j.bcmd.2014.07.021

• Late-onset SCD
• Mosaicism
• Loss of heterozygosity
• 11p15 isoparental isodisomy

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 beta(A) peak at Sanger direct sequencing and a semi-quantitative FRET Light Cycler method which showed a low expression of the beta(A) allele compared to the beta(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.

• 出版日期2015-1