Shwachman Diamond Syndrome: a multidisciplinary approach to better understand the pathogenesis and clinical implications

Introduction: Shwachman Diamond syndrome (SDS) is an autosomal recessive condition that is attributed to mutations in SBDS gene. Due to the functionally versatile nature of SBDS protein, the effects due to mutations in SBDS gene are reflected at cellular level and clinically as diverse phenotypes. Material and Methods: In this study, we analyzed karyotype instability and chromosomal aberrations that take place in SDS patients’ bone marrow (BM) by techniques like karyotyping, fluorescent in situ hybridization and comparative genomic hybridization array. We also carried out a comparative BM and osteoblasts gene expression pattern of SDS patients with healthy controls using expression arrays. Lastly, we exploited the ability of ataluren to restore SBDS nonsense mutation. Results: We found that all twenty five SDS patients that we studied for karyotype instability carried del(20)(q) in their BM, where EIF6 gene was lost unanimously and interstitially. The gene expression pattern of the SDS patients BM and osteoblasts was quite different than the healthy controls. The use of ataluren apparently restored the nonsense mutation in SBDS gene. Conclusion: We highlighted the loss of EIF6 in del(20)(q) by SDS patients that acts as a mechanism to compensate the deficiency of SBDS. It was also established that the gene expression pattern of SDS patients is different than the healthy controls. We also demonstrated the apparent potential of ataluren as a therapeutic option for SDS.