EXPRESSION STUDIES IN BONE MARROW OF PATIENTS WITH SHWACHMAN-DIAMOND SYNDROME CARRYING A CHROMOSOME 20 LONG ARMS INTERSTITIAL DELETION

The most frequent chromosome anomalies acquired in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS) are an isochromosome for the long arms of chromosome 7, i(7)(q10), and an interstitial deletion of the long arms of chromosome 20, del(20)(q). In our cohort of 89 patients, 14 bear the i(7)(q10), 12 the del(20)(q), and 3 both the changes. We found that in the patients with the i(7)(q10) two copies of the mild mutation 258+2T>C were present on the isochromosome. As to the del(20)(q), we obtained evidence that the gene EIF6 is lost in all the patients analysed, leading to hemizygosity in the BM clone: the consequent reduced amount of EIF6 protein would facilitate ribobiogenesis. So, both the most frequent anomalies seem to work as a kind of rescue mechanism for the ribosomopathy in BM through copy number and expression variation of either SBDS gene (at 7q11.21) or EIF6 gene (at 20q11.22). We collected RNA from the BM of 5 patients: 3 carrying the del(20)(q) in variable clonal percentages, 1 with the i(7)(q10) in a low proportion of cells, and 1 carrying a different chromosome anomaly. We performed quantitative RT-PCR for expression analysis of the EIF6 gene, and we performed an array-based whole transcriptome analisys in order to focus on possible differences between the patients carrying the del(20)(q) and the other ones. These assays showed a clearcut EIF6 hypoexpression in the patients carrying the del(20)(q). As to the overall expression pattern of genes of haematopoiesis, it seems more similar to controls than to other SDS patients. From the results of this preliminary study that involved only a few patients, we confirm that EIF6 loss consequent to the deletion del(20)(q), acquired in BM, could really represent a rescue mechanism for the clone carrying the anomaly