Cytogenetic and molecular evidence of constitutional mosaic trisomy 8 and hematologic abnormalities in a phenotypically normal woman. J. Meck, T.J. Chen, L-J. Wong, J. Imholte, K. Perry, N. Qin, S. Baidas. Georgetown Univ Med Ctr, Wash, DC.

   Trisomy 8 has clinical significance as both a constitutional and an acquired abnormality. As a constitutional abnormality the phenotype ranges from normal to severe. Trisomy 8 is also an acquired chromosome abnormality common in myeloid disorders. Individuals with constitutional mosaic trisomy 8 regardless of phenotype are predisposed to develop cancer, most often myelodysplastic syndrome. Our report is significant because genotype analysis was used to show that the trisomy was constitutional in our patient and because she presented with hematologic abnormalities, but not cancer. Our patient is a phenotypically normal 34 year old woman with recurrent oral aphtous ulcers since childhood and increased MCV in the last several years. Bone marrow biopsy was slightly hypocellular with mild megaloblastic changes, but otherwise normal morphologically. Unexpectedly, the bone marrow karyotype revealed trisomy 8 in all 20 metaphases analyzed. A 72 hour PHA stimulated peripheral blood culture had 14/20 trisomy 8 cells; the 24 hour culture had no metaphases. None of the 50 skin fibroblast metaphases were trisomic. Constitutional trisomy 8 mosaicism with the abnormal cells confined to blood/bone marrow would explain the lack of phenotypic abnormalities with the exception of hematologic problems. It is unclear whether her bone marrow findings represent an increased risk for development of myelodysplastic syndrome. To confirm the trisomy as constitutional, we performed genotype analysis using six chromosome 8 genetic markers (heterozygosity 0.73 -0.87). Fluorescent labeled PCR primers were used to amplify microsatellite loci. Allele number and size were determined by GeneScan analysis on an ABI 377. All 6 markers suggested the presence of 3 alleles. Three markers showed 3 different sized alleles, while the other 3 markers showed 2 different sized alleles with a ratio clearly indicative of a trisomy. These results are consistent with our patient having a constitutional trisomy mosaicism resulting from a meiotic error with trisomy rescue. Parental genotyping will be performed for confirmation.