Advances in genome-wide molecular cytogenetics allow identification of novel 
submicroscopic DNA copy number alterations (aCNAs) and copy-neutral loss of 
heterozygosity (cnLOH) resulting in homozygosity for known gene mutations in 
myeloid neoplasms. We describe the use of an oligo-SNP array for genomic 
profiling of aCNA and cnLOH, together with sequence analysis of recurrently 
mutated genes, in a patient with myelodysplastic syndrome (MDS) presenting with 
normal karyotype and FISH results. Oligo-SNP array analysis revealed a 
hemizygous deletion of 896 kb at chromosome 5q31.2, representing the smallest 5q 
deletion reported to date. The deletion involved multiple genes, including two 
tumor suppressor candidate genes (CTNNA1 and HSPA9) that are associated with 
MDS/AML. The SNP-array study also detected 3 segments of somatic cnLOH: one 
involved the entire long arm of chromosome 4; the second involved the distal 
half of the long arm of chromosome 7, and the third encompassed the entire 
chromosome 22 (UPD 22). Sequence analysis revealed mutations in TET2 (4q), EZH2 
(7q), ASXL1 (20q11.21), and RUNX1 (21q22.3). Coincidently, TET2 and EZH2 were 
located at segments of cnLOH resulting in their homozygosity. Loss of 
heterozygosity affecting these two chromosomes and mutations in TET2 and EZH2 
are indicative of a myelodysplastic syndrome with a poor prognosis. Deletion of 
the tumor suppressor genes CTNNA1 and HSPA9 is also likely to contribute to a 
poor prognosis. Furthermore, the original cnLOHs in multiple chromosomes and 
additional cnLOH 14q in the follow-up study suggest genetic evolution of the 
disease and poor prognosis. This study attests to the fact that some patients 
with a myelodysplastic syndrome who exhibit a normal karyotype may have 
underlying genetic abnormalities detectable by chromosomal microarray and/or 
targeted mutation analyses.