Mutation profile of BBS genes in patients with Bardet-Biedl syndrome : An Italian study

Background: Bardet-Biedl syndrome (BBS) is a rare inherited multisystemic disorder with autosomal recessive or complex digenic triallelic inheritance. There is currently no treatment for BBS, but some morbidities can be managed. Accurate molecular diagnosis is often crucial for the definition of appropriate patient management and for the development of a potential personalized therapy. Methods: We developed a next-generation-sequencing (NGS) protocol for the screening of the 18 most frequently mutated genes to define the genotype and clarify the mutation spectrum of a cohort of 20 BBS Italian patients. Results: We defined the causative variants in 60% of patients; four of those are novel. 33% of patients also harboured variants in additional gene/s, suggesting possible oligogenic inheritance. To explore the function of different genes, we looked for correlations between genotype and phenotype in our cohort. Hypogonadism was more frequently detected in patients with variants in BBSome proteins, while renal abnormalities in patients with variations in BBSome chaperonin genes. Conclusions: NGS is a powerful tool that can help understanding BBS patients' phenotype through the identification of mutations that could explain differences in phenotype severity and could provide insights for the development of targeted therapy. Furthermore, our results support the existence of additional BBS loci yet to be identified

Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations

Background: Heterozygous mutations in OPA1 are a common cause of autosomal dominant optic atrophy, sometimes associated with extra-ocular manifestations. Few cases harboring compound heterozygous OPA1 mutations have been described manifesting complex neurodegenerative disorders in addition to optic atrophy. Results: We report here three patients: one boy showing an early-onset mitochondrial disorder with hypotonia, ataxia and neuropathy that was severely progressive, leading to early death because of multiorgan failure; two unrelated sporadic girls manifesting a spastic ataxic syndrome associated with peripheral neuropathy and, only in one, optic atrophy. Using a targeted resequencing of 132 genes associated with mitochondrial disorders, in two probands we found compound heterozygous mutations in OPA1: in the first a 5 nucleotide deletion, causing a frameshift and insertion of a premature stop codon (p.Ser64Asnfs*7), and a missense change (p.Ile437Met), which has recently been reported to have clinical impact; in the second, a novel missense change (p.Val988Phe) co-occurred with the p.Ile437Met substitution. In the third patient a homozygous mutation, c.1180G > A (p.Ala394Thr) in OPA1 was detected by a trio-based whole exome sequencing approach. One of the patients presented also variants in mitochondrial DNA that may have contributed to the peculiar phenotype. The deleterious effect of the identified missense changes was experimentally validated in yeast model. OPA1 level was reduced in available patients\u2019 biological samples, and a clearly fragmented mitochondrial network was observed in patients\u2019 fibroblasts. Conclusions: This report provides evidence that bi-allelic OPA1 mutations may lead to complex and severe multi-system recessive mitochondrial disorders, where optic atrophy might not represent the main feature

Survey context and question wording affects self reported annoyance due to road traffic noise: a comparison between two cross-sectional studies

<p>Abstract</p> <p>Background</p> <p>Surveys are a common way to measure annoyance due to road traffic noise, but the method has some draw-backs. Survey context, question wording and answer alternatives could affect participation and answers and could have implications when comparing studies and/or performing pooled analyses. The aim of this study was to investigate the difference in annoyance reporting due to road traffic noise in two types of surveys of which one was introduced broadly and the other with the clearly stated aim of investigating noise and health.</p> <p>Methods</p> <p>Data was collected from two surveys carried out in the municipality of Malmö, southern Sweden in 2007 and 2008 (n = 2612 and n = 3810). The first survey stated an aim of investigating residential environmental exposure, especially noise and health. The second survey was a broad public health survey stating a broader aim. The two surveys had comparable questions regarding noise annoyance, although one used a 5-point scale and the other a 4-point scale. We used geographic information systems (GIS) to assess the average road and railway noise (L_Aeq,24h) at the participants' residential address. Logistic regression was used to calculate odds ratios for annoyance in relation to noise exposure.</p> <p>Results</p> <p>Annoyance at least once a week due to road traffic noise was significantly more prevalent in the survey investigating environment and health compared to the public health survey at levels > 45 dB(A), but not at lower exposure levels. However no differences in annoyance were found when comparing the extreme alternatives "never" and "every day". In the study investigating environment and health, "Noise sensitive" persons were more likely to readily respond to the survey and were more annoyed by road traffic noise compared to the other participants in that survey.</p> <p>Conclusions</p> <p>The differences in annoyance reporting between the two surveys were mainly due to different scales, suggesting that extreme alternatives are to prefer before dichotomization when comparing results between the two. Although some findings suggested that noise-sensitive individuals were more likely to respond to the survey investigating noise and health, we could not find convincing evidence that contextual differences affected either answers or participation.</p

Genetic characteristics of 234 Italian patients with macular and cone/cone-rod dystrophy

Two-hundred and thirty-four Italian patients with a clinical diagnosis of macular, cone and cone-rod dystrophies (MD, CD, and CRD) were examined using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and—when necessary—multiplex ligation-dependent probe amplification (MLPA) to diagnose the molecular cause of the aforementioned diseases. When possible, segregation analysis was performed in order to confirm unsolved cases. Each patient’s retinal phenotypic characteristics were determined using focal and full-field ERGs, perimetry, spectral domain optical coherence tomography and fundus autofluorescence. We identified 236 potentially causative variants in 136 patients representing the 58.1% of the total cohort, 43 of which were unpublished. After stratifying the patients according to their clinical suspicion, the diagnostic yield was 62.5% and 53.8% for patients with MD and for those with CD/CRD, respectively. The mode of inheritance of all cases confirmed by genetic analysis was 70% autosomal recessive, 26% dominant, and 4% X-linked. The main cause (59%) of both MD and CD/CRD cases was the presence of variants in the ABCA4 gene, followed by variants in PRPH2 (9%) and BEST1 (6%). A careful morpho-functional evaluation of the phenotype, together with genetic counselling, resulted in an acceptable diagnostic yield in a large cohort of Italian patients. Our study emphasizes the role of targeted NGS to diagnose MDs, CDs, and CRDs, as well as the clinical usefulness of segregation analysis for patients with unsolved diagnosis

Introduzione

Lo scritto descrive il quadro di riferimento entro cui si colloca la pubblicazione del volume, che documenta il lavoro di ricerca sul patrimonio di edifici residenziali realizzati a Buenos Aires, a cavallo tra il XIX e il XX secolo, da architetti, ingegneri e costruttori italiani

Carlos Morra e il disegno degli edifici scolastici a Buenos Aires come strumento di azione politica e culturale. Carlos Morra and the design of schoolhouses in Buenos Aires, as an instrument of a political and cultural action.

Il contributo documenta l'indagine, nel quadro di una più ampia ricerca per la conoscenza e valorizzazione del patrimonio architettonico realizzato a Buenos Aires da progettisti italiani, incentrata sullo studio dei principi architettonici definiti dall’architetto e ingegnere militare Carlos Morra (1854-1926), di origini campane e formazione torinese, nel disegno dei 23 edifici scolastici edificati a Buenos Aires tra il 1885 e il 1904, nel quadro del Plan de Edificación Escolar, fondamentale strumento di attuazione delle politiche d’integrazione sociale e culturale poste alla base della formazione della giovane Repubblica Argentina.The research, as a part of a broader project, aimed at understanding and enhancing the architectural heritage by Italian designers in Buenos Aires , focuses on the study of architectural rules defined by the architect and military engineer Carlos Morra (1854-1926) – born in Campania, but trained in Turin - in his design of 23 schoolhouses, built in Buenos Aires between 1885 and 1904, in the framework of the Plan de Edificación Escolar, a fundamental instrument for carrying out the social and cultural integration policies, on whitch the constitutive structure of young Argentinian Republic was based

Cromatismi a Buenos Aires, tra riferimenti identitari e strategie di riqualificazione.

Il contributo affronta il ruolo dell'elemento cromatico nel processo di costruzione della città di Buenos Aires e la valenza identitaria da esso assunta, nella definizione sia del volto complessivo della città nella fase di sua trasformazione in Capital federal e sia dei caratteri peculiari delle singole parti di cui essa si compone. L'analisi è stata condotta con riferimento sia ai principali edifici pubblici e collettivi e sia al patrimonio edilizio a destinazione residenziale. Descrive inoltre il ruolo del colore rispetto ai problemi di conservazione e tutela di tale patrimonio, analizzando alcuni casi studio - come quello degli edifici pubblici a La Boca e gli interventi sulle facciate di calle Lanín - in cui l'elemento cromatico ha costituito il principale strumento dei processi di recupero architettonico e urbano