Abstract
Shwachman-Diamond syndrome SDS (MIM 260400) is an autosomal recessive disorder. Characterized by exocrine insufficiency of the pancreas, bone marrow hypoplasia resulting in cytopenias, especially neutropenia, variable degree of skeletal abnormalities, failure to thrive, and increasing risk of developing myelodysplasia or transformation to leukemia. SDS is mainly caused by Shwachman Bodian Diamond Syndrome gene (MIM ID 607444). SBDS gene is 14899 bp in length, located in chromosome seven in the eleventh region of the long arm, and is composed of five exons. It's a ribosomal maturation factor which encodes a highly conservative protein that has widely unknown functions despite of its abundance in the nucleolus. A total number of 53 SNPs of homo sapiens SBDS gene were obtained from the national center for biotechnology information (NCBI) analyzed using translational tools, 7 of which were deleterious according to SIFT server and were further analyzed using several softwares (Polyhen-2, SNPs&Go, I-Mutant 2.0, Mutpred2, structural analysis soft wares and multiple sequence alignment tool). Four SNPs (rs11557408 (V17M), rs11557409 (R11H), rs367842164 (A66T), and rs376960114 (F57S)) were predicted to be disease causing, localized at highly conservative regions of the SBDS protein and were not reported in any previous study. In addition, the study predicts new functions of the SBDS protein DNA related, and suggests explanations for Patients developing cytopenias and failure to thrive through genetic coexpression and physical interaction with RBF1 and EXOSC3, respectively.
