Molecular Modelling and Dynamics Study of nsSNP in STXBP1 Gene in Early Infantile Epileptic Encephalopathy Disease.

Early Infantile Epileptic Encephalopathy (known as Ohtahara Syndrome) is one of the most severe and earliest forms of epilepsy, characterized by early seizures onset. It affects newborns and children between two and six years old. Among the genes that have been associated with early infantile epileptic encephalopathy, the STXBP1 gene, which encodes the Syntaxin binding protein1a that is involved in SNARE complex formation, contributes to synaptic vesicles exocytosis. The aim of this study was to identify the most pathogenic polymorphisms of STXBP1 gene and determine their impact on the structure and stability of Stxbp1 protein. The high-risk nonsynonymous single nucleotide polymorphisms (nsSNPs) in the STXBP1 gene were predicted using 13 bioinformatics tools. The conservation analysis was realized by CONSURF web server. The analysis of the impact of the pathogenic SNPs on the structure of Stxbp1 protein was realized using YASARA software, and the molecular dynamics simulation was performed using GROMACS software. Out of 245 nsSNPs, we identified 11 (S42P, H103D R190W, R235G, D238E, L256P, P335S, C354Y, L365V, R406C, and G544D) as deleterious using in silico prediction tools. Conservation analysis results revealed that all these nsSNPs were located in conserved regions. The comparison of the hydrogen and hydrophobic interactions in the wild type Stxbp1 structure and its mutant forms showed that all these nsSNPs affect the protein structure on different levels. The molecular dynamics simulations revealed that the total of nsSNPs affect the protein stability, residual fluctuation, and the compaction at different levels. This study provides helpful information on high risk nsSNPs that may affect the Stxbp1 protein structure and function. Thus, these variants should be taken into consideration during the genetic screening of patients suffering from early infantile epileptic encephalopathy.

AZF microdeletions and partial deletions of AZFc region on the Y chromosome in Moroccan men / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To evaluate for the first time the frequency of Y chromosome microdeletions and the occurrence of the partial deletions of AZFc region in Moroccan men, and to discuss the clinical significance of AZF deletions.</p><p><b>METHODS</b>We screened Y chromosome microdeletions and partial deletions of the AZFc region of a consecutive group of infertile men (n = 149) and controls (100 fertile men, 76 normospermic men). AZFa, AZFb, AZFc and partial deletions of the AZFc region were analyzed by polymerase chain reaction (PCR) according to established protocols.</p><p><b>RESULTS</b>Among the 127 infertile men screened for microdeletion, four subjects were found to have microdeletions: two AZFc deletions and two AZFb+AZFc deletions. All the deletions were found only in azoospermic subjects (4/48, 8.33%). The overall AZFc deletion frequency was low (4/127, 3.15%). AZF microdeletions were not observed in either oligoasthenoteratozoospermia (OATS) or the control. Partial deletions of AZFc (gr/gr) were observed in a total of 7 of the 149 infertile men (4.70%) and 7 partial AZFc deletions (gr/gr) were found in the control group (7/176, 3.98%). In addition, two b2/b3 deletions were identified in two azoospermic subjects (2/149, 1.34%) but not in the control group.</p><p><b>CONCLUSION</b>Our results suggest that the frequency of Y chromosome AZF microdeletions is elevated in individuals with severe spermatogenic failure and that gr/gr deletions are not associated with spermatogenic failure.</p>