On the Impact of Ambient Humidity and Evaporation on Demixing of Binary Mixtures.

As per known data, hexane and diethylene glycol monoethyl ether (DGME) are perfectly miscible at temperatures above some 6 °C (critical solution temperature, CST), manifesting a miscibility gap below this temperature. Yet, when deposing hexane-DGME layers or sessile droplets, we unexpectedly observe demixing already at room temperature. As hexane is volatile, one may be tempted to explain this in terms of evaporative cooling. However, apart from some extreme cases, estimations and direct measurements reveal that such cooling cannot be as drastic as to bring the temperature down to CST. Then, we hypothesize that such anomalous demixing could be caused by moisture in the ambient atmosphere. After all, even if hexane is practically immiscible with water, DGME is hygroscopic. To verify this conjecture, a series of experiments were carried out in a chamber with well-controlled temperature and relative humidity (RH), where a layer of the hexane-DGME mixture was observed by reflective shadowgraphy. In this way, we could measure the "apparent" CST as a function of RH, which indeed proves to be higher than 6 °C and tends to the classical value only at vanishing RH. Our picture of the phenomenon is also well backed up by a heuristic model of the ternary mixture (also including water) based on regular-solution and van Laar fits of the known binary-pair properties.

Combination therapy (desmopressin plus oxybutynin) improves the response rate compared with desmopressin alone in patients with monosymptomatic nocturnal enuresis and nocturnal polyuria and absence of constipation predict the response to this treatment.

Combination therapy (CT) (desmopressin plus oxybutynin) has been considered for the treatment of monosymptomatic nocturnal enuresis (MNE). We designed our study with the aim to evaluate the response rate to CT compared with desmopressin alone (primary outcome) and to identify factors associated with the response to CT (secondary outcome). We prospectively enrolled children with MNE with absent/partial response after 3 months of evening treatment with 240 mcg of desmopressin. We defined the response rate to CT compared with desmopressin alone according to the standardization of terminology document of the International Children's Continence Society: no-response, < 50% reduction; partial response, 50 to 99% reduction; and complete response, 100% reduction of wet nights. Both partial response and complete response to CT were clustered for the analyses of this manuscript. The enrolled children treated with 240 mcg/evening of desmopressin had also an additional evening administration of 0.3 mg/kg oxybutynin. A follow-up was scheduled at 3 and 6 months after the beginning of CT. At 3 months, oxybutynin dose was augmented to 0.5 mg/kg in case of absent/partial response to CT. Nocturnal diuresis was measured in 5 wet nights prior the beginning of therapy with desmopressin. Nocturnal polyuria (NP) was defined as nocturnal urine production > 130% of the expected bladder capacity. All patients with constipation were treated with macrogol. We enrolled 81 children (35.8% females) with a mean age of 8.4 ± 2.3 years. Seventy-eight patients completed the follow-up. After the CT, 59/78 (75.6%) patients showed an improvement of the response with CT compared with desmopressin alone. At multivariate analysis, both NP in more than 1 night (OR = 8.5; 95% CI, 1.4-51.6; p = 0.02) and absence of constipation (OR = 7.1; 95% CI, 1.6-31.0; p = 0.009) resulted significant after Bonferroni correction. CONCLUSIONS: CT determines an improvement of response compared to therapy with desmopressin alone in 75.6% of patients. Significant predictive factors of response to CT were presence of NP and absence of constipation. WHAT IS KNOWN: • Combination therapy (CT) (desmopressin plus anticholinergic drug) has been described as a therapeutic option for patients with monosymptomatic nocturnal enuresis (MNE) not responding to desmopressin alone as first-line treatment. • Variable protocols and variable combination of drugs have been described with a response rate ranging from 44 to 76%. WHAT IS NEW: • We found that 59 patients (75.6%) treated with evening administration of 240 mcg of sublingual desmopressin plus 0.3-0.5 mg/kg of oxybutynin had an improvement of response compared to treatment with desmopressin alone. • We add evidence that presence of frequently recurring nocturnal polyuria and absence of constipation are predictors of response to CT.

Deciphering the Role of Wnt and Rho Signaling Pathway in iPSC-Derived ARVC Cardiomyocytes by In Silico Mathematical Modeling.

Arrhythmogenic Right Ventricular cardiomyopathy (ARVC) is an inherited cardiac muscle disease linked to genetic deficiency in components of the desmosomes. The disease is characterized by progressive fibro-fatty replacement of the right ventricle, which acts as a substrate for arrhythmias and sudden cardiac death. The molecular mechanisms underpinning ARVC are largely unknown. Here we propose a mathematical model for investigating the molecular dynamics underlying heart remodeling and the loss of cardiac myocytes identity during ARVC. Our methodology is based on three computational models: firstly, in the context of the Wnt pathway, we examined two different competition mechanisms between ß-catenin and Plakoglobin (PG) and their role in the expression of adipogenic program. Secondly, we investigated the role of RhoA-ROCK pathway in ARVC pathogenesis, and thirdly we analyzed the interplay between Wnt and RhoA-ROCK pathways in the context of the ARVC phenotype. We conclude with the following remark: both Wnt/ß-catenin and RhoA-ROCK pathways must be inactive for a significant increase of PPARγ expression, suggesting that a crosstalk mechanism might be responsible for mediating ARVC pathogenesis.

FGFR Fusions in Cancer: From Diagnostic Approaches to Therapeutic Intervention.

Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors involved in many biological processes. Deregulated FGFR signaling plays an important role in tumor development and progression in different cancer types. FGFR genomic alterations, including FGFR gene fusions that originate by chromosomal rearrangements, represent a promising therapeutic target. Next-generation-sequencing (NGS) approaches have significantly improved the discovery of FGFR gene fusions and their detection in clinical samples. A variety of FGFR inhibitors have been developed, and several studies are trying to evaluate the efficacy of these agents in molecularly selected patients carrying FGFR genomic alterations. In this review, we describe the most frequent FGFR aberrations in human cancer. We also discuss the different approaches employed for the detection of FGFR fusions and the potential role of these genomic alterations as prognostic/predictive biomarkers.

Outcome for Conservative Surgery for the Correction of Severe Mitral Valve Regurgitation in Children: A Single-Center Experience.

Evolving reconstructive techniques have progressively become the preferred approach for treatment of pediatric mitral valve regurgitation. We present our experience in a cohort of patients undergoing surgical correction for severe mitral regurgitation. Fifty-five patients (age 1 month-18 years; median 5 years) were included in the present analysis. Different surgical techniques were used (posterior leaflet augmentation in 25, isolated cleft closure in 12, Alfieri-type procedure in 10, annuloplasty in 5, with artificial chordae in 2, and quadrangular resection with chordal transposition in 1). Follow-up time ranged from 1 to 192 months (median 38[IQR 12-54] months). Operative and follow-up mortality was 0%. Reintervention in the whole population occurred in 31% of patients. However, when first surgery was performed under 2 years of age (no = 17), reintervention reached nearly 50%. The degree of residual mitral regurgitation at follow-up remained stable after surgery, while a significant increase in mean transmitral gradient was observed over time (paired t test = 0.03). In multivariable Cox-regression analysis, post-surgical transmitral gradient was the only independent predictor for reintervention (p = 0.017; HR 2.4; 95%CI 1.2-5.1), after correcting for differences in age at surgery, type of reintervention, mitral annulus dimension, and BSA at the first surgery. ROC curve demonstrated that a post-surgical transmitral mean gradient value > 5 mmHg, was predictive for reintervention (AUC = 0.89; Youden index = 0.44). Our study suggests that the use of conservative technique strategy achieves satisfactory functional results in infants and children with severe MR, although the rate of reoperation in younger patients remains substantial. Post-operative moderate mitral stenosis was the strongest predictor for reoperation.

Left Ventricular Mass Indexing in Infants, Children, and Adolescents: A Simplified Approach for the Identification of Left Ventricular Hypertrophy in Clinical Practice.

OBJECTIVE: To determine a simplified method to identify presence of left ventricular hypertrophy (LVH) in pediatric populations because the relationship between heart growth and body growth in children has made indexing difficult for younger ages. STUDY DESIGN: Healthy children (n = 400; 52% boys, 0-18 years of age) from 2 different European hospitals were studied to derive a simplified formula. Left ventricular mass (LVM) was calculated according to the Devereux formula. The derived approach to index LVM was tested on a validation cohort of 130 healthy children from a different hospital center. RESULTS: There was a strong nonlinear correlation between height and LVM. LVM was best related to height to a power of 2.16 with a correction factor of 0.09. Analysis of residuals for LVM/[(height(2.16)) + 0.09] showed an homoscedastic distribution in both sexes throughout the entire height range. A partition value of 45 g/m(2.16) was defined as the upper normal limit for LVM index. As opposed to formula suggested by current guidelines (ie, LVM/height(2.7)) when applying the proposed approach in the validation cohort of 130 healthy participants, no false positives for LVH were found (0% vs 8%; P < .01). CONCLUSIONS: Our data support the possibility to have a single partition (ie, 45 g/m(2.16)) value across the whole pediatric age range to identify LVH, without the time-consuming need of computing specific percentiles for height and sex.

Diagnostic Accuracy of Lung Ultrasound in Neonatal Diseases: A Systematized Review.

Background: Respiratory problems are frequent in newborns, and are mainly studied with chest X-rays, whereas CT scans are usually needed for the evaluation of rare malformations and diseases. Lung ultrasound (LUS] has been proposed as an alternative method of diagnosing a variety of respiratory conditions. In recent years, there has been a rapid increase in LUS studies, thanks to the ability of LUS to rapidly exclude complications and significantly reduce radiation exposure in this fragile population. We aimed to summarize the current knowledge about LUS. Methods: A literature search was conducted on the Medline and Cochrane databases using appropriate terms. The inclusion criteria were: English language and human species. Exclusion criteria were: non-English language, animal species, case reports, case series, non-systematic reviews, and editorials. Results: The search returned 360 results. No Cochrane reviews were found. Titles and abstracts were screened, and 37 were finally considered. Studies concerning the use of lung ultrasound for the following conditions were presented: neonatal respiratory distress syndrome, transient tachypnea of the newborn, pneumothorax, pulmonary hemorrhage, pneumonia, bronchopulmonary dysplasia, and prediction of extubation success. Conclusions: We discussed the utility of LUS for the diagnosis and treatment of neonatal diseases according to the most recent literature.

Molecular diagnostics and personalized medicine in oncology: challenges and opportunities.

Increasing evidence demonstrates that target-based agents are active only in molecularly selected populations of patients. Therefore, the identification of predictive biomarkers has become mandatory to improve the clinical development of these novel drugs. Mutations of the epidermal growth factor receptor (EGFR) or rearrangements of the ALK gene in non-small-cell lung cancer, and BRAF mutations in melanoma are clear examples of driver mutations and predictive biomarkers of response to treatment with specific inhibitors. Predictive biomarkers might also identify subgroups of patients that are not likely to respond to specific drugs, as shown for KRAS mutations and anti-EGFR monoclonal antibodies in colorectal carcinoma. The discovery of novel driver molecular alterations and the availability of drugs capable to selectively block such oncogenic mechanisms are leading to a rapid increase in the number of putative biomarkers that need to be assessed in each single patient. In this respect, two different approaches are being developed to introduce a comprehensive molecular characterization in clinical practice: high throughput genotyping platforms, which allow the detection of recognized genetic aberrations in clinical samples, and next generation sequencing that can provide information on all the different types of cancer-causing alterations. The introduction of these techniques in clinical practice will increase the possibility to identify molecular targets in each individual patient, and will also allow to follow the molecular evolution of the disease during the treatment. By using these approaches, the development of personalized medicine for patients with cancer will finally become possible.

The Impact of COVID-19 Pandemic Lockdown on the Relationship between Pediatric MAFLD and Renal Function.

BACKGROUND: Both direct and indirect effects of COVID-19 have been found in all age groups. In particular, adult data demonstrated significant changes in patients with chronic and metabolic disease (e.g., obesity, diabetes, chronic kidney disease (CKD), and metabolic associated fatty liver dysfunction (MAFLD)), while similar pediatric evidence is still limited. We aimed at investigating the impact of the COVID-19 pandemic lockdown on the relationship between MAFLD and renal function in children with CKD due to congenital abnormalities of the kidney and urinary tract (CAKUT). METHODS: A total of 21 children with CAKUT and CKD ≥ stage 1 underwent a comprehensive evaluation within 3 months before and 6 months after the first Italian lockdown. RESULTS: At follow-up, CKD patients with MAFLD presented higher BMI-SDS, serum uric acid, triglycerides, and microalbuminuria levels and lower eGFR levels than those without MAFLD (all p < 0.05). Higher ferritin and white blood cell concentrations were also found in patients with CKD diagnosed with MAFLD than peers without MAFLD (both p = 0.01). Compared to children without MAFLD, a higher delta of BMI-SDS, eGFR levels, and microalbuminuria levels was found in patients with MAFLD. CONCLUSIONS: Due to the negative influence of the COVID-19 lockdown on cardiometabolic health in childhood, a careful management of children with CKD is warranted.

Gut microbiota and COVID-19: An intriguing pediatric perspective.

Gastrointestinal (GI) involvement has been reported in approximately 50% of patients with coronavirus disease 2019 (COVID-19), which is due to the pathogenic role of inflammation and the intestinal function of the angiotensin-converting enzyme 2 and its receptor. Accumulating adult data has pointed out that gut dysbiosis might occur in these patients with a potential impact on the severity of the disease, however the role of gut microbiota in susceptibility and severity of COVID-19 disease in children is still poorly known. During the last decades, the crosstalk between gut and lung has been largely recognized resulting in the concept of "gut-lung axis" as a central player in modulating the development of several diseases. Both organs are involved in the common mucosal immune system (including bronchus-associated and gut-associated lymphoid tissues) and their homeostasis is crucial for human health. In this framework, it has been found that the role of GI dysbiosis is affecting the homeostasis of the gut-liver axis. Of note, a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects, but it remains to be clarified. Based on the increased risk of inflammatory diseases in children with COVID-19, the potential correlation between gut microbiota dysfunction and COVID-19 needs to be studied in this population. We aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.

First identification of bovine hepacivirus in wild boars.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma in humans. Humans were long considered the only hosts of Hepacivirus. Recently HCV-like sequences have been found in several animal species. Hepaciviruses are considered species-specific but a wider host range and a zoonotic role has been hypothesized. We report the first detection of bovine hepacivirus (BovHepV) sequences in wild boars. A total of 310 wild boars hunted in Campania region were investigated with a pan-hepacivirus nested-PCR protocol for the NS3 gene. Hepacivirus RNA was detected in 5.8% of the animals. Sequence and phylogenetic analysis showed high homology with BovHepV subtype F, with nucleotide identity of 99%. The positive wild boars were georeferenced, revealing high density of livestock farms, with no clear distinction between animal husbandry and hunting areas. These findings might suggest the ability of BovHepV to cross the host-species barrier and infect wild boars.

Left ventricle dysfunction in patients with critical neonatal pulmonary stenosis: echocardiographic predictors. A single-center retrospective study.

Background: The aim of this study is to identify echocardiographic predictors of transient left ventricle dysfunction after pulmonary valve balloon dilatation (PVBD), in neonates with pulmonary valve stenosis (PVS) and atresia with intact septum (PAIVS) at birth. Methods: The study includes patients admitted at the Bambino Gesù Children Hospital from January 2012 to January 2017. Clinical, echocardiographic and cardiac catheterization data before and after PVBD were retrospectively analyzed. Results: Twenty-nine infants were included in the study (21 male and eight female). The median age was 5.8 ± 7.1 days. Eight patients developed transient LV dysfunction (three PAIVS and five PVS) and comparing data before and after the procedure, there was no difference in right ventricle geometrical and functional parameters except for evidence of at least moderate pulmonary valve regurgitation after PVBD. Conclusion: Moderate to severe degree pulmonary valve regurgitation was significant associated to LV dysfunction (p < 0.05) in PVS and PAIVS patients.

Involvement of herpesviruses in cases of abortion among water buffaloes in southern Italy.

A six-year study on water buffaloes from the Campania Region (Southern Italy) was conducted to evaluate the presence of bovine/bubaline herpesviruses in cases of abortion. A total of 244 buffalo foetuses were analysed by real-time PCR to detect the presence of: bovine alphaherpesvirus 1(BoHV-1), bubaline alphaherpesvirus 1 (BuHV-1), bovine alphaherpesvirus 2 (BuHV-2), and bovine gammaherpesvirus 4 (BoHV-4). The foetuses of 14 water buffaloes that showed abortions were positive for BuHV-1 (4 animals) and/or BoHV-4 (11 animals), with one of these cases showing co-infection with BuHV-1 and BoHV-4. This study reports the first identification of BoHV-4 in water buffaloes. Cases of abortion were analysed using both molecular and cultural assays for the presence of other pathogens. In nearly all the abortion cases positive for BoHV-4, the virus was identified as a co-infecting agent together with other microorganisms, whereas in two abortion cases, it was the only pathogen found.

Promising Role of Circulating Tumor Cells in the Management of SCLC.

Small cell lung cancer is an aggressive disease for which few therapeutic options are currently available. Although patients initially respond to therapy, they rapidly relapse. Up to today, no biomarkers for guiding treatment of SCLC patients have been identified. SCLC patients rarely undergo surgery and often the available tissue samples are inadequate for biomarker analysis. Circulating tumor cells (CTCs) are rare cells in the peripheral blood that might be used as surrogates of tissue samples. Different methodological approaches have been developed for studies of CTCs in SCLC. In addition to CTC count, which might provide prognostic and predictive information, genomic and transcriptomic analyses allow the characterization of molecular profiles of CTCs and permit the study of tumor heterogeneity. The employment of CTC-derived xenografts offers complementary information to genomic analyses and CTC enumeration about the mechanisms involved in the sensitivity/resistance to treatments. Using these approaches, CTC analysis is providing relevant information on SCLC biology that might aid in the development of personalized therapeutic strategies for SCLC patients.

SARS-CoV-2 quantitative real time PCR and viral loads analysis among asymptomatic and symptomatic patients: an observational study on an outbreak in two nursing facilities in Campania Region (Southern Italy).

BACKGROUND: In December 2019 an outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 was first observed in Wuhan, China. The virus has spread rapidly throughout the world creating a pandemic scenario. Several risk factors have been identified, such as age, sex, concomitant diseases as well as viral load. A key point is the role of asymptomatic people in spreading SARS-CoV-2. An observational study in Southern Italy was conducted in order to elucidate the possible role of asymptomatic individuals related to their viral loads in the transmission of the virus within two nursing facilities. METHODS: Oro-nasopharyngeal swabs from 179 nursing health care workers and patients were collected. SARS-CoV-2 RT-qPCR was performed and viral loads were calculated by using standard curve. A statistical correlation between viral loads, the presence/absence of symptoms, age and sex variables was investigated. RESULTS: SARS-CoV-2 was confirmed in the 50.8 % (n = 91) of the cases. Median age of positive individuals resulted higher than negative ones. Over 65 year as well as female individuals showed higher susceptibility to SARS-CoV-2 infection, OR = 3.93 and 2.86, respectively. Among 91 tested positive, the 70.3 % was symptomatic while the 29.7 % was asymptomatic. Median viral loads of asymptomatic individuals were found statistically significant higher than symptomatic ones (p = 0.001), while no influence was observed in age and sex variables. The presence of comorbidities was 8.9 folds higher in patients who showed and developed symptoms compared to non-symptomatic ones. Moreover, higher viral loads were found in patients who remained asymptomatic than pre-symptomatic (p = 0.022). CONCLUSIONS: A range from 9.2 to 69 % of confirmed SARS-CoV-2 cases remains asymptomatic, moreover, sporadic transmissions from asymptomatic people are reported, that makes their involvement an important issue to take into account in the spreading control of the virus. An asymptomatic clinical course was observed in the 29.7 % of positive individuals, moreover, median viral loads resulted to be statistically significant when compared to symptomatic ones. Surely, such a relevant frequency should not be ignored in relation to the spread of the disease in an environment which has not only important intrinsic (age, sex, concomitant diseases) but also extrinsic factors such as high population density and close contacts.

Generation of human induced pluripotent stem cell lines (UNIMGi003-A and UNIMGi004-A) from two Italian siblings affected by Unverricht-Lundborg disease.

Unverricht-Lundborg disease (ULD) is an inherited form of progressive myoclonus epilepsy caused by mutations in the gene encoding Cystatin B (CSTB), an inhibitor of lysosomal proteases. The most common mutation described in ULD patients is an unstable expansion of a dodecamer sequence located in the CSTB gene promoter. This expansion is causative of the downregulation of CSTB gene expression and, consequently, of its inhibitory activity. Here we report the generation of induced pluripotent stem cell (iPSC) lines from two Italian siblings having a family history of ULD and affected by different clinical and pathological phenotypes of the disease.

Prevalence of Infection with Porcine Circovirus Types 2 and 3 in the Wild Boar Population in the Campania Region (Southern Italy).

In recent years, porcine circovirus (PCV) infection has been documented as an important and emerging health concern for livestock and wildlife worldwide. The purpose of the present study was to assess the molecular prevalence of PCV-2 and PCV-3 and to clarify the epidemiological role of wild boars in the circulation of this virus in Campania, Southern Italy. For this purpose, samples from several organs were collected during the hunting season 2017-2018 from 148 wild boars in the Campania region. Quantitative real-time PCR was used for the detection and quantification of PCV-2 and PCV-3 genomes. The combined prevalence of PCV-2 and PCV-3 was 74.32% in the wild boars tested. The proportions of wild boars positive for PCV-2 or PCV-3, or coinfected, were 47.30%, 49.32%, and 22.30%, respectively. No link was detected between PCV positivity and location, but gender was a risk factor for the disease (female; p < 0.0001; OR 0.29). Furthermore, our study provides a snapshot of PCV-2 and PCV-3 circulation in wild boars in the Campania region: our findings can help us to better understand the role of wildlife in PCV circulation.

Colorectal cancer genomic biomarkers in the clinical management of patients with metastatic colorectal carcinoma.

Colorectal carcinoma (CRC) is an heterogeneous disease in which different genetic alterations play a role in its pathogenesis and progression and offer potential for therapeutic intervention. The research on predictive biomarkers in metastatic CRC (mCRC) mainly focused on the identification of biomarkers of response or resistance to anti-epidermal growth factor receptor monoclonal antibodies. In this respect, international guidelines suggest testing mCRC patients only for KRAS, NRAS and BRAF mutations and for microsatellite instability. However, the use of novel testing methods is raising relevant issue related to these biomarkers, such as the presence of sub-clonal RAS mutations or the clinical interpretation of rare no-V600 BRAF variants. In addition, a number of novel biomarkers is emerging from recent studies including amplification of ERBB2, mutations in ERBB2, MAP2K1 and NF1 and rearrangements of ALK, ROS1, NTRK and RET. Mutations in POLE and the levels of tumor mutation burden also appear as possible biomarkers of response to immunotherapy in CRC. Finally, the consensus molecular subtypes classification of CRC based on gene expression profiling has prognostic and predictive implications. Integration of all these information will be likely necessary in the next future in order to improve precision/personalized medicine in mCRC patients.

First Detection of Listeria monocytogenes in a Buffalo Aborted Foetus in Campania Region (Southern Italy).

Listeria monocytogenes (LM) is the causative agent of listeriosis in both animals and humans, representing one of the most severe food-borne diseases in humans. Out of 13 serotypes, only three (i.e., 1/2a, 1/2b, and 4b) are responsible for 95% of human outbreaks of listeriosis. Ruminants have been hypothesised to represent the main natural reservoir for this pathogen and to be involved in the transmission of Listeria to humans. During pregnancy, listeriosis in ruminants cause various reproductive disorders as well as abortion. However, little is known about abortion due to LM in water buffaloes (Bubalus bubalis). In this study, we report for the first time the detection of LM in a water buffalo foetus in the region of Campania, Italy. Complete necropsy was performed, and samples and swabs from the abomasum, kidneys, liver, lungs, and spleen were collected. Microbiological and molecular analyses were carried out to detect bacterial, viral, and protozoarian abortive pathogens. The results revealed the presence of LM in the liver, lungs, and abomasum, and no other agent was detected. Isolation was confirmed by biochemical and molecular tests. Molecular serotype characterisation was performed, and serogroup IVb was identified. In conclusion, because of the zoonotic implications of our findings, this report highlights the importance of including LM in the diagnostic panel in cases of bubaline abortion.

Generation of iPSC lines from two patients affected by febrile seizure due to inherited missense mutation in SCN1A gene.

Here, we described the generation of human induced pluripotent stem cell lines (hiPSCs) from fibroblasts isolated by punch biopsies of two siblings carrying inherited mutation (c.434 T > C) in the SCN1A gene, encoding for the neuronal voltage gated sodium channel NaV1.1. The mutation leads to the substitution of a highly conserved methionine with a threonine (M145T) in the protein sequence, leading to infant febrile seizures (FS). The older brother, affected by complex FS, also developed temporal lobe epilepsy (TLE) during adolescence.