Cytogenetic and a-CGH monitoring in Shwachman-Diamond syndrome.

Since 1999 we follow a cohort of patients affected with Shwachman-Diamond syndrome (SDS)asto cytogenetics: their number is now 71. We performed array-based Comparative Genomic Hybridization (a-CGH) in 24 of them. The a-CGH was applied to bone marrow (BM) DNA in all cases, and also on DNA from peripheral blood (PB) in two patients. Repeated analyses were made in eight cases. All results were compared with standard cytogenetics and fluorescent in situ hybridization (FISH) assays. Main relevant issues concerned the following points. - The isochromosomei(7)(q10), one of the most frequent anomalies in BM of SDS patients, was studied by a-CGH in 7 patients, with a definite contribution to precise how the i(7)(q10) is built up. - In 2 patients the i(7)(q10) was found also in DNA from PB: the proportion of abnormal cells was comparable to neutrophils percentage, thus indicating that mature circulating neutrophils bear the anomaly. - In 6 patients the other frequent anomaly, the interstitial deletion int del(20)(q11.21q13.32), was defined by a-CGH as to breakpoints and loss of material, which included in all cases the region of the locus EIF6. - Other peculiar imbalances were found: a tinyint del(20) undetected by other techniques, together with the i(7)(q10) in a small clone; in 2 patients a further rearrangement of the int del(20)(q11.21q13.32), with a similar patterns in both, including two duplicated regions;in one patient a peculiar cytogenetic evolution,with normal karyotype, then with the i(7)(q10), and subsequently with a myelodysplastic syndrome associated with a complex karyotype; in one patient a deletion of chromosome 6 was shown by a-CGH to be a translocation t(3;6)(q24;q13). - In 10 patients the results of a-CGH failed to show chromosome imbalances, detected in 9/10 with the other techniques, due to the paucity of the abnormal clone.