Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD

Pathogenic variants in INPP5E cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in INPP5E. Additional two patients showed early onset IRD with limited JBTS features. Detailed phenotypic description for all probands is presented. We report 14 rare INPP5E variants, 12 of which have not been reported in previous studies. We present tertiary protein modeling and analyze all INPP5E variants for deleteriousness and phenotypic correlation. We observe that the combined impact of INPP5E variants in JBTS and non-syndromic IRD patients does not reveal a clear genotype–phenotype correlation, suggesting the involvement of genetic modifiers. Our study cements the wide phenotypic spectrum of INPP5E disease, adding proof that sequence defects in this gene can lead to early-onset non-syndromic IRD

Y box binding protein 1 (YB-1) oncoprotein at the hub of DNA proliferation, damage and cancer progression

The Y Box binding protein 1 (YB-1) belongs to the highly conserved Cold Shock Domain protein family and is a major component of messenger ribonucleoprotein particles (mRNPs) in various organisms and cells. Cold Shock proteins are multifunctional nucleic acids binding proteins involved in a variety of cellular functions. Biological activities of YB-1 range from the regulation of transcription, splicing and translation, to the orchestration of exosomal RNA content. The role of YB-1 in malignant cell transformation and fate transition is the subject of intensive investigation. Besides, emerging evidence indicates that YB-1 participates in several DNA damage repair pathways as a non-canonical DNA repair factor thus pointing out that the protein can allow cancer cells to evade conventional anticancer therapies and avoid cell death. Here, we will attempt to collect and summarize the current knowledge on this subject and provide the basis for further lines of inquiry

CRYSRULER: an Integrated System of Computer Programs for Crystal Structure Analysis on Personal Computers

A system of programs and routines is presented that is expressly designed to be user friendly, as much as possible, and to give the real possibility of performing all the stages of crystallographic computation on a personal computer. The package has been developed in a modular way to support adapted versions of some popular crystallographic programs, such as MULTAN, SHELX, PLUTO, ORTEP and PARST. Original facilities are provided for file and system management and molecular graphics on screen display, plotter and matrix printer. The result is a powerful menu-assisted package, which represents the first example of an independent crystallographic work station running under the MS–DOS operating system. The package has been implemented on an IBM AT and can be used without modifications on any XT/AT-compatible personal computer