The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations. Conclusions This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.

Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen

Human endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5' LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis

Urediospores of rust fungi are ice nucleation active at > -10°C and harbor ice nucleation active bacteria

Various features of the biology of the rust fungi and of the epidemiology of the plant diseases they cause illustrate the important role of rainfall in their life history. Based on this insight we have characterized the ice nucleation activity (INA) of the aerially disseminated spores (urediospores) of this group of fungi. Urediospores of this obligate plant parasite were collected from natural infections of 7 species of weeds in France, from coffee in Brazil and from field and greenhouse-grown wheat in France, the USA, Turkey and Syria. Immersion freezing was used to determine freezing onset temperatures and the abundance of ice nuclei in suspensions of washed spores. Microbiological analyses of spores from France, the USA and Brazil, and subsequent tests of the ice nucleation activity of the bacteria associated with spores were deployed to quantify the contribution of bacteria to the ice nucleation activity of the spores. All samples of spores were ice nucleation active, having freezing onset temperatures as high as −4 °C. Spores in most of the samples carried cells of ice nucleation-active strains of the bacterium Pseudomonas syringae (at rates of less than 1 bacterial cell per 100 urediospores), but bacterial INA accounted for only a small fraction of the INA observed in spore suspensions. Changes in the INA of spore suspensions after treatment with lysozyme suggest that the INA of urediospores involves a polysaccharide. Based on data from the literature, we have estimated the concentrations of urediospores in air at cloud height and in rainfall. These quantities are very similar to those reported for other biological ice nucleators in these same substrates. However, at cloud level convective activity leads to widely varying concentrations of particles of surface origin, so that mean concentrations can underestimate their possible effects on clouds. We propose that spatial and temporal concentrations of biological ice nucleators active at temperatures > −10 °C and the specific conditions under which they can influence cloud glaciation need to be further evaluated so as to understand how evolutionary processes could have positively selected for INA.