CDHR1 mutations in retinal dystrophies

We report ophthalmic and genetic findings in patients with autosomal recessive retinitis pigmentosa (RP), cone-rod dystrophy (CRD) or cone dystrophy (CD) harboring potential pathogenic variants in the CDHR1 gene. Detailed ophthalmic examination was performed in seven sporadic and six familial subjects. Mutation screening was done using a customized next generation sequencing panel targeting 105 genes implicated in inherited retinal disorders. In one family, homozygosity mapping with subsequent candidate gene analysis was performed. Stringent filtering for rare and potentially disease causing variants following a model of autosomal recessive inheritance led to the identification of eleven different CDHR1 variants in nine index cases. All variants were novel at the time of their identification. In silico analyses confirmed their pathogenic potential. Minigene assays were performed for two non-canonical splice site variants and revealed missplicing for the mutant alleles. Mutations in CDHR1 are a rare cause of retinal dystrophy. Our study further expands the mutational spectrum of this gene and the associated clinical presentation

Allelic Expression Imbalance in the Human Retinal Transcriptome and Potential Impact on Inherited Retinal Diseases

Inherited retinal diseases (IRDs) are often associated with variable clinical expressivity (VE) and incomplete penetrance (IP). Underlying mechanisms may include environmental, epigenetic, and genetic factors. Cis-acting expression quantitative trait loci (cis-eQTLs) can be implicated in the regulation of genes by favoring or hampering the expression of one allele over the other. Thus, the presence of such loci elicits allelic expression imbalance (AEI) that can be traced by massive parallel sequencing techniques. In this study, we performed an AEI analysis on RNA-sequencing (RNA-seq) data, from 52 healthy retina donors, that identified 194 imbalanced single nucleotide polymorphisms(SNPs) in 67 IRD genes. Focusing on SNPs displaying AEI at a frequency higher than 10%, we found evidence of AEI in several IRD genes regularly associated with IP and VE (BEST1, RP1, PROM1, and PRPH2). Based on these SNPs commonly undergoing AEI, we performed pyrosequencing in an independent sample set of 17 healthy retina donors in order to confirm our findings. Indeed, we were able to validate CDHR1, BEST1, and PROM1 to be subjected to cis-acting regulation. With this work, we aim to shed light on differentially expressed alleles in the human retina transcriptome that, in the context of autosomal dominant IRD cases, could help to explain IP or VE.Peer reviewe

On the Representation of Orthogonally Additive Polynomials in l(p)

We present a new proof of a Sundaresan's result which shows that the space of orthogonally additive polynomials P-0((k)l(p)) is isometrically isomorphic to l(p/p-k) if k < p < infinity and to l(infinity) if 1 <= p <= k

On the multilinear trigonometric problem of moments

A multilinear generalization of the trigonometric problem of moments is presented and discussed. The moments c(k), k is an element of Z(n) of a regular Borel polymeasure gamma on T(n) are characterized by means of a norm parallel to . parallel to(omega) on functions on Z(n). Some properties of this norm are analyzed and various examples are presented showing that it is strictly weaker than the Frechet norms and the absolute convergence norm. The convolution product of multilinear functionals is defined and an inverse theorem is proved

Opportunistic Genetic Screening for Familial Hypercholesterolemia in Heart Transplant Patients

Heart transplantation remains the gold standard for the treatment of advanced heart failure (HF). Identification of the etiology of HF is mandatory, as the specific pathology can determine subsequent treatment. Early identification of familial hypercholesterolemia (FH), the most common genetic disorder associated with premature cardiovascular disease, has a potential important impact on clinical management and public health. We evaluated the genetic information in the genes associated with FH in a cohort of 140 heart-transplanted patients. All patients underwent NGS genetic testing including LDLR, APOB, and PCSK9. We identified four carriers of rare pathogenic variants in LDLR and APOB. Although all four identified carriers had dyslipidemia, only the one carrying the pathogenic variant LDLR c.676T&gt;C was transplanted due to CAD. Another patient with heart valvular disease was carrier of the controversial LDLR c.2096C&gt;T. Two additional patients with non-ischemic dilated cardiomyopathy were carriers of variants in APOB (c.4672A&gt;G and c.5600G&gt;A). In our cohort, we identified the genetic cause of FH in patients that otherwise would not have been diagnosed. Opportunistic genetic testing for FH provides important information to perform personalized medicine and risk stratification not only for patients but also for relatives at concealed high cardiovascular risk. Including the LDLR gene in standard NGS cardiovascular diagnostics panels should be considered

Trends in cetacean sightings along the Galician coast, north-western Spain, 2003 2007, and inferences about cetacean habitat preferences

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Characterization of Left Ventricular Non-Compaction Cardiomyopathy

Left ventricle non-compaction cardiomyopathy (LVNC) has gained great interest in recent years, being one of the most controversial cardiomyopathies. There are several open debates, not only about its genetic heterogeneity, or about the possibility to be an acquired cardiomyopathy, but also about its possible overdiagnosis based on imaging techniques. In order to better understand this entity, we identified 38 LVNC patients diagnosed by cardiac MRI (CMRI) or anatomopathological study that could underwent NGS-sequencing and clinical study. Anatomopathological exam was performed in eight available LVNC hearts. The genetic yield was 34.2%. Patients with negative genetic testing had better left ventricular ejection fraction (LVEF) or it showed a tendency to improve in follow-up, and a possible trigger factor for LVNC was identified in 1/3 of them. Nonetheless, cerebrovascular accidents occurred in similar proportions in both groups. We conclude that in LVNC there seem to be different ways to achieve the same final phenotype. Genetic testing has a good genetic yield and provides valuable information. LVNC without an underlying genetic cause may have a better prognosis in terms of LVEF evolution. However, anticoagulation to prevent cerebrovascular accident (CVA) should be carefully evaluated in all patients. Larger series with pathologic examination are needed to help better understand this entity

Is Iberian harbour porpoise (Phocoena phocoena) threatened by interactions with fisheries?

International audienceHarbour porpoises in the Iberian Peninsula form a genetically distinct, small (around 2900 animals) and isolated population. Their main prey are commercially important fish, hence overlap between porpoise occurrence and fishing activity is almost inevitable. We compile information on bycatch mortality, mainly collected over the last 15 years, based on on-board and land-based monitoring of fishing activity, analysis of cause of death and mortality rate based on strandings, and interview surveys with fishers. All these sources provide data of questionable reliability, for example due to low and incomplete coverage of fleets by on-board observers (indeed, essentially an absence of such data for the north coast of Spain (ICES area 8e). Nevertheless, all available estimates appear to suggest that the number of porpoises killed annually is likely to be unsustainably high. Despite some apparent incompatibility between abundance data, estimated bycatch mortality rates and genetic data, we suggest that both new mitigation action to reduce bycatch and improved monitoring are needed to secure the future of this population