Correction to: Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia.

The original version of this article unfortunately contained mistake in Fig. 3 image.

Biallelic Variants in the Nuclear Pore Complex Protein NUP93 Are Associated with Non-progressive Congenital Ataxia.

Nuclear pore complexes (NPCs) are the gateways of the nuclear envelope mediating transport between cytoplasm and nucleus. They form huge complexes of 125 MDa in vertebrates and consist of about 30 different nucleoporins present in multiple copies in each complex. Here, we describe pathogenic variants in the nucleoporin 93 (NUP93) associated with an autosomal recessive form of congenital ataxia. Two rare compound heterozygous variants of NUP93 were identified by whole exome sequencing in two brothers with isolated cerebellar atrophy: one missense variant (p.R537W) results in a protein which does not localize to NPCs and cannot functionally replace the wild type protein, whereas the variant (p.F699L) apparently supports NPC assembly. In addition to its recently described pathological role in steroid-resistant nephrotic syndrome, our work identifies NUP93 as a candidate gene for non-progressive congenital ataxia.

VarGenius executes cohort-level DNA-seq variant calling and annotation and allows to manage the resulting data through a PostgreSQL database.

BACKGROUND: Targeted resequencing has become the most used and cost-effective approach for identifying causative mutations of Mendelian diseases both for diagnostics and research purposes. Due to very rapid technological progress, NGS laboratories are expanding their capabilities to address the increasing number of analyses. Several open source tools are available to build a generic variant calling pipeline, but a tool able to simultaneously execute multiple analyses, organize, and categorize the samples is still missing. RESULTS: Here we describe VarGenius, a Linux based command line software able to execute customizable pipelines for the analysis of multiple targeted resequencing data using parallel computing. VarGenius provides a database to store the output of the analysis (calling quality statistics, variant annotations, internal allelic variant frequencies) and sample information (personal data, genotypes, phenotypes). VarGenius can also perform the "joint analysis" of hundreds of samples with a single command, drastically reducing the time for the configuration and execution of the analysis. VarGenius executes the standard pipeline of the Genome Analysis Tool-Kit (GATK) best practices (GBP) for germinal variant calling, annotates the variants using Annovar, and generates a user-friendly output displaying the results through a web page. VarGenius has been tested on a parallel computing cluster with 52 machines with 120GB of RAM each. Under this configuration, a 50 M whole exome sequencing (WES) analysis for a family was executed in about 7 h (trio or quartet); a joint analysis of 30 WES in about 24 h and the parallel analysis of 34 single samples from a 1 M panel in about 2 h. CONCLUSIONS: We developed VarGenius, a "master" tool that faces the increasing demand of heterogeneous NGS analyses and allows maximum flexibility for downstream analyses. It paves the way to a different kind of analysis, centered on cohorts rather than on singleton. Patient and variant information are stored into the database and any output file can be accessed programmatically. VarGenius can be used for routine analyses by biomedical researchers with basic Linux skills providing additional flexibility for computational biologists to develop their own algorithms for the comparison and analysis of data. The software is freely available at: https://github.com/frankMusacchia/VarGenius.

Expanding the histopathological spectrum of CFL2-related myopathies.

Congenital myopathies (CMs) caused by mutation in cofilin-2 gene (CFL2) show phenotypic heterogeneity ranging from early-onset and rapid progressive forms to milder myopathy. Muscle histology is also heterogeneous showing rods and/or myofibrillar changes. Here, we report on three new cases, from two unrelated families, of severe CM related to novel homozygous or compound heterozygous loss-of-function mutations in CFL2. Peculiar histopathological changes showed nemaline bodies and thin filaments accumulations together to myofibrillar changes, which were evocative of the muscle findings observed in Cfl2-/- knockout mouse model.

The possible correlation between the chronic esophageal achalasia and periodontal disease - a pilot study.

OBJECTIVE: Achalasia is a very rare disease characterized by the lack of motor coordination in various phases of contraction-relaxation of esophageal muscles. The aim of the study is to determine the correlation between esophageal achalasia and oral diseases. PATIENTS AND METHODS: Thirteen esophageal achalasia patients were assessed for the presence of any potential oral symptoms through a questionnaire. 5 volunteered to be included in the study. The oral health status of these 5 patients was assessed by a clinical oral examination. The oral health status of the included cases was compared to the oral health status data from a published observational study on healthy individuals belonging to the same (Italian) population. RESULTS: Our results show that the number of periodontal pockets with Probing Pocket Dept > 4 mm is significantly increased, compared to the average of the Italian population; the Bleeding On Probing (BOP) is not related to the Plaque Control Record (PCR); so we can say that the value of periodontal index is not correlated with the value of oral hygiene index. CONCLUSIONS: Considering the limitations of a research based on small numbers, it nevertheless seems advisable to assert that there is a correlation between esophageal achalasia and periodontal disease.

Timing for implant placement in patients treated with radiotherapy of head and neck.

BACKGROUND: Aim of this retrospective study was to evaluate the most appropriate timing for the implant placement in oral cancer patients treated with radiation therapy. MATERIALS AND METHODS: We collected data for 17 subjects (10 females, 7 males; mean age: 51 ± 19) with malignant oral tumors who had been treated with ablative surgery and radiation therapy of head and neck. The radiotherapy was set in accordance with the NCCN guidelines. Every patient received dental implant rehabilitation between 2014 and 2016. A total of 84 titanium implants were placed, at a minimum interval of 12 months, in irradiated residual bone. Every patient underwent a minimum follow-up of 12 months. RESULT: Implant loss was dependent on the position and location of the implants (P = 0.05-0.1). Moreover, implant survival was dependent on the total dose of radiation and, mostly, on the timing of implant insertion after the end of the radiation therapy. This result was highly statistically significant (P < 0.01). Whether the implant was loaded is another highly significant (P < 0.01) factor determining survival. We observed significantly better outcomes when the implant was placed at least after 14 months and not loaded until at least 6 months after placement. CONCLUSION: Although the retrospective design of this study could be affected by selection and information biases, we conclude that a delayed implant placement after the end of the radiation therapy and a delayed loading protocol will give the best chance of implant osseointegration, stability and, ultimately, effective dental rehabilitation.

Implant placement in oral squamous cells carcinoma patients treated with chemoradiotherapy: "Sapienza Head and Neck Unit" clinical recommendations.

OBJECTIVE: To date, the treatment of patients affected by head and neck squamous cell carcinoma (HNSCC) is highly challenging for clinicians. Possible therapies are surgical resection of the tumor mass, radiotherapy, chemotherapy or, more often, a combined treatment that inevitably affects both normal and tumor cells. Consequently, patients' anatomy and functions become reduced or altered. Nowadays the functional restoration is significantly improved thanks to the innovation in prosthetic rehabilitation and in radiotherapy. The current IMRT (Intensity Modulated Radiation Therapy) allows planning adequate treatments evaluating different tissues' involvement and radiation dosage. It is possible to define the most suitable sites for implant insertion, using data provided by dose-volume histogram (DVH). This study aims to illustrate the idea of obtaining a unique CT image by blending radiation-planning CT and Cone Beam CT. PATIENTS AND METHODS: Five patients among 54 candidates were selected for this study. Selection criteria were: good general health (PS0-1), age between 18 and 72 years, absence of metastatic disease or local recurrence, disease-free interval of at least 18 months. Radiation planning CT scan and maxillo-facial CT Cone Beam of every patient were overlapped and merged. Only one CT for every evaluated patient was obtained in order to plan the most suitable areas for implant placement. RESULTS: The placement of 10 implants in 5 patients was programmed using the explained method. Patients (all male) were aged between 48 and 72 years old, with a median age of 64.4 years. In every case of this study, a modification of the initial program of implant placement was necessary. The new imaging method we are proposing was able to provide information about radiation isodoses received in the planned osseointegrated implants' positions. CONCLUSIONS: This new method allows operators to correct their own therapy plans and choices, customizing the treatment plan on the actual condition of the patient. Moreover, it makes all the rehabilitation process safer and can reduce the risk of failure, side effects and inconveniences for the patients.

Pleomorphic adenoma rehabilitative treatment in growing up patient: a 20-years follow-up.

OBJECTIVE: Although tumors of minor salivary glands are rare, the pleomorphic adenoma is the most common pathology among the benign neoplasm and can be found with high prevalence in the junction between hard palate and soft palate. Most of the maxillary tumors are surgically treated through either a total or partial maxillectomy. However, surgical defects lead to both clinical and psychologic disorders for the patient. A postoperative obturator prosthesis is a good option in patients who underwent maxillectomy. It allows to restore both masticatory and speaking functions, as well as aesthetic appearance. When reconstruction of the surgical site is possible, an implant-supported prosthesis can be considered to guarantee a better function and aesthetic's rehabilitation. CASE REPORT: This clinical report presents the prosthetic rehabilitation of a patient who underwent maxillectomy because of a pleomorphic adenoma of hard palate minor salivary glands. The patient was treated with a palatal obturator prosthesis first and with an implant-supported prosthesis after surgical site's reconstruction and complete healing. CONCLUSIONS: The rehabilitation of the patient after maxillectomy through both these devices was an excellent option and provided clinical benefits, improving the patient's quality of life, allowing the patient's reinsertion into society.

Plant adaptation to dynamically changing environment: the shade avoidance response.

The success of competitive interactions between plants determines the chance of survival of individuals and eventually of whole plant species. Shade-tolerant plants have adapted their photosynthesis to function optimally under low-light conditions. These plants are therefore capable of long-term survival under a canopy shade. In contrast, shade-avoiding plants adapt their growth to perceive maximum sunlight and therefore rapidly dominate gaps in a canopy. Daylight contains roughly equal proportions of red and far-red light, but within vegetation that ratio is lowered as a result of red absorption by photosynthetic pigments. This light quality change is perceived through the phytochrome system as an unambiguous signal of the proximity of neighbors resulting in a suite of developmental responses (termed the shade avoidance response) that, when successful, result in the overgrowth of those neighbors. Shoot elongation induced by low red/far-red light may confer high relative fitness in natural dense communities. However, since elongation is often achieved at the expense of leaf and root growth, shade avoidance may lead to reduction in crop plant productivity. Over the past decade, major progresses have been achieved in the understanding of the molecular basis of shade avoidance. However, uncovering the mechanisms underpinning plant response and adaptation to changes in the ratio of red to far-red light is key to design new strategies to precise modulate shade avoidance in time and space without impairing the overall crop ability to compete for light.