Forecasting potential invaders to prevent future biological invasions worldwide.

The ever-increasing and expanding globalisation of trade and transport underpins the escalating global problem of biological invasions. Developing biosecurity infrastructures is crucial to anticipate and prevent the transport and introduction of invasive alien species. Still, robust and defensible forecasts of potential invaders are rare, especially for species without known invasion history. Here, we aim to support decision-making by developing a quantitative invasion risk assessment tool based on invasion syndromes (i.e., generalising typical attributes of invasive alien species). We implemented a workflow based on 'Multiple Imputation with Chain Equation' to estimate invasion syndromes from imputed datasets of species' life-history and ecological traits and macroecological patterns. Importantly, our models disentangle the factors explaining (i) transport and introduction and (ii) establishment. We showcase our tool by modelling the invasion syndromes of 466 amphibians and reptile species with invasion history. Then, we project these models to amphibians and reptiles worldwide (16,236 species [c.76% global coverage]) to identify species with a risk of being unintentionally transported and introduced, and risk of establishing alien populations. Our invasion syndrome models showed high predictive accuracy with a good balance between specificity and generality. Unintentionally transported and introduced species tend to be common and thrive well in human-disturbed habitats. In contrast, those with established alien populations tend to be large-sized, are habitat generalists, thrive well in human-disturbed habitats, and have large native geographic ranges. We forecast that 160 amphibians and reptiles without known invasion history could be unintentionally transported and introduced in the future. Among them, 57 species have a high risk of establishing alien populations. Our reliable, reproducible, transferable, statistically robust and scientifically defensible quantitative invasion risk assessment tool is a significant new addition to the suite of decision-support tools needed for developing a future-proof preventative biosecurity globally.

Commonalities and differences in injured patient experiences of accessing and receiving quality injury care: a qualitative study in three sub-Saharan African countries.

OBJECTIVES: To understand commonalities and differences in injured patient experiences of accessing and receiving quality injury care across three lower-income and middle-income countries. DESIGN: A qualitative interview study. The interviews were audiorecorded, transcribed and thematically analysed. SETTING: Urban and rural settings in Ghana, South Africa and Rwanda. PARTICIPANTS: 59 patients with musculoskeletal injuries. RESULTS: We found five common barriers and six common facilitators to injured patient experiences of accessing and receiving high-quality injury care. The barriers encompassed issues such as service and treatment availability, transportation challenges, apathetic care, individual financial scarcity and inadequate health insurance coverage, alongside low health literacy and information provision. Facilitators included effective information giving and informed consent practices, access to health insurance, improved health literacy, empathetic and responsive care, comprehensive multidisciplinary management and discharge planning, as well as both informal and formal transportation options including ambulance services. These barriers and facilitators were prevalent and shared across at least two countries but demonstrated intercountry and intracountry (between urbanity and rurality) variation in thematic frequency. CONCLUSION: There are universal factors influencing patient experiences of accessing and receiving care, independent of the context or healthcare system. It is important to recognise and understand these barriers and facilitators to inform policy decisions and develop transferable interventions aimed at enhancing the quality of injury care in sub-Saharan African nations.

Use of Vascular Shunt at the Time of Pancreatectomy with Venous Resection: A Systematic Review.

BACKGROUND: The rising diffusion of vascular resections during complex pancreatectomy for malignancy, for both oncological and technical matters, brought with it the use of vascular shunts, either temporary or definitive, to prevent bowel congestion and liver ischemia. This study aimed to systematically review the literature on the technical feasibility of vascular shunts during advanced pancreatic surgery, analyzing intraoperative and postoperative outcomes. METHODS: A systematic literature search was performed on PubMed, Scopus, Web of Science, and the Cochrane Library Central, according to PRISMA guidelines. Studies published before 2006 were excluded, considering the lack of a standardized definition of locally advanced pancreatic cancer. The main outcomes evaluated were the overall complication rate and shunt patency. RESULTS: Among 789 papers retrieved from the database search, only five fulfilled the inclusion criteria and were included in the review, amounting to a total of 145 patients undergoing a shunt creation at the time of pancreatectomy. Pancreatic adenocarcinoma (PDAC) was found to be the most common diagnosis and pancreaticoduodenectomy was the main surgical procedure, accounting for 88% and 83% of the overall cohort, respectively. The distal splenorenal shunt was the most performed. Overall, 44 out of 145 patients (30%) experienced postoperative complications; the long-term patency of definitive shunts was 83% (110 out of 120 patients). CONCLUSIONS: An increasing number of patients with borderline resectable or locally advanced PDAC are becoming amenable to resection and shunt creation may facilitate vascular resection with clear margins, becoming a valid tool of modern pancreatic surgery.

Exploring the priorities of ageing populations in Pakistan, comparing views of older people in Karachi City and Thatta.

As a lower middle-income country, Pakistan faces multiple issues that influence the course of healthy ageing. Although there is some understanding of these issues and the objective health outcomes of people in Pakistan, there is less knowledge on the perceptions, experiences, and priorities of the ageing population and their caretakers (hereafter, "stakeholders"). The aim of the study was to identify the needs and priorities of older adults and stakeholders across both urban and rural locations. We sought to explore the views of two groups of people, older adults and stakeholders on topics including the definition of ageing as well as areas of importance, services available, and barriers to older people living well. Two-day workshops were conducted in one rural city, Thatta and one urban city, Karachi. The workshops were designed using the Nominal Group Technique, which included plenary and roundtable discussions. The responses were ranked through rounds of voting and a consensus priority list was obtained for each topic and group. Responses were categorized using the socio-ecological framework. Responses were compared between stakeholders and older people and between different geographical areas. 24 urban and 26 rural individuals aged over 60 years and 24 urban and 26 rural stakeholders attended the workshops. There were few areas of agreement with respect to both geographical region and participant group. Comparing older adults' definition of ageing, there was no overlap between the top five ranked responses across urban and rural locations. With respect to areas of importance, there was agreement on free health care as well as financial support. In terms of barriers to healthy ageing, only nation-wide inflation was ranked highly by both groups. In addition, there were relatively few areas of congruence between stakeholder and older adult responses, irrespective of location, although engagement with family, adequate nutrition and monetary benefits were responses ranked by both groups as important for healthy ageing. Both groups ranked issues with the pension system and financial difficulties as barriers. When categorized using the socio-ecological model, across all questions, societal factors were prioritized most frequently (32 responses), followed by individual (27), relationship (15), and environment (14). Overcoming barriers to facilitate healthy ageing will require a multi-faceted approach and must incorporate the priorities of older individuals. Our results may serve as a guide for researchers and policymakers for future engagement and to plan interventions for improving the health of the ageing population in Pakistan.

Study of the effects of pasteurization and selected microbial starters on functional traits of fermented table olives.

Table olives are one of the most known fruit consumed as fermented food, being a fundamental component of the Mediterranean diet. Their production and consumption continue to increase globally and represent an important economic source for the producing countries. One of the most stimulating challenges for the future is the modernization of olive fermentation process. Besides the demand for more reproducible and safer production methods that could be able to reduce product losses and potential risks, producers and consumers are increasingly attracted by the final product characteristics and properties on human health. In this study, the contribution of microbial starters to table olives was fully described in terms of specific enzymatic and microbiological profiles, nutrient components, fermentation-derived compounds, and content of bioactive compounds. The use of microbial starters from different sources was tested considering their technological features and potential ability to improve the functional traits of fermented black table olives. For each fermentation assay, the effects of controlled temperature (kept at 20 °C constantly) versus not controlled environmental conditions (oscillating between 7 and 17 °C), as well as the consequences of the pasteurization treatment were tested on the final products. Starter-driven fermentation strategies seemed to increase both total phenolic content and total antioxidant activity. Herein, among all the tested microbial starters, we provide data indicating that two bacterial strains (Leuconostoc mesenteroides KT 5-1 and Lactiplantibacillus plantarum BC T3-35), and two yeast strains (Saccharomyces cerevisiae 10A and Debaryomyces hansenii A15-44) were the better ones related to enzyme activities, total phenolic content and antioxidant activity. We also demonstrated that the fermentation of black table olives under not controlled environmental temperature conditions was more promising than the controlled level of 20 °C constantly in terms of technological and functional properties considered in this study. Moreover, we confirmed that the pasteurization process had a role in enhancing the levels of antioxidant compounds.

Loss-of-function variants in ERF are associated with a Noonan syndrome-like phenotype with or without craniosynostosis.

Pathogenic, largely truncating variants in the ETS2 repressor factor (ERF) gene, encoding a transcriptional regulator negatively controlling RAS-MAPK signaling, have been associated with syndromic craniosynostosis involving various cranial sutures and Chitayat syndrome, an ultrarare condition with respiratory distress, skeletal anomalies, and facial dysmorphism. Recently, a single patient with craniosynostosis and a phenotype resembling Noonan syndrome (NS), the most common disorder among the RASopathies, was reported to carry a de novo loss-of-function variant in ERF. Here, we clinically profile 26 individuals from 15 unrelated families carrying different germline heterozygous variants in ERF and showing a phenotype reminiscent of NS. The majority of subjects presented with a variable degree of global developmental and/or language delay. Their shared facial features included absolute/relative macrocephaly, high forehead, hypertelorism, palpebral ptosis, wide nasal bridge, and low-set/posteriorly angulated ears. Stature was below the 3rd centile in two-third of the individuals, while no subject showed typical NS cardiac involvement. Notably, craniosynostosis was documented only in three unrelated individuals, while a dolichocephalic aspect of the skull in absence of any other evidence supporting a premature closing of sutures was observed in other 10 subjects. Unilateral Wilms tumor was diagnosed in one individual. Most cases were familial, indicating an overall low impact on fitness. Variants were nonsense and frameshift changes, supporting ERF haploinsufficiency. These findings provide evidence that heterozygous loss-of-function variants in ERF cause a "RASopathy" resembling NS with or without craniosynostosis, and allow a first dissection of the molecular circuits contributing to MAPK signaling pleiotropy.

Defining the variant-phenotype correlation in patients affected by Noonan syndrome with the RAF1:c.770C>T p.(Ser257Leu) variant.

Hypertrophic cardiomyopathy (HCM) is the major contributor to morbidity and mortality in Noonan syndrome (NS). Gain-of-function variants in RAF1 are associated with high prevalence of HCM. Among these, NM_002880.4:c.770C > T, NP_002871.1:p.(Ser257Leu) accounts for approximately half of cases and has been reported as associated with a particularly severe outcome. Nevertheless, comprehensive studies on cases harboring this variant are missing. To precisely define the phenotype associated to the RAF1:c.770C > T, variant, an observational retrospective analysis on patients carrying the c.770C > T variant was conducted merging 17 unpublished patients and literature-derived ones. Data regarding prenatal findings, clinical features and cardiac phenotypes were collected to provide an exhaustive description of the associated phenotype. Clinical information was collected in 107 patients. Among them, 92% had HCM, mostly diagnosed within the first year of life. Thirty percent of patients were preterm and 47% of the newborns was admitted in a neonatal intensive care unit, mainly due to respiratory complications of HCM and/or pulmonary arterial hypertension. Mortality rate was 13%, mainly secondary to HCM-related complications (62%) at the average age of 7.5 months. Short stature had a prevalence of 91%, while seizures and ID of 6% and 12%, respectively. Two cases out of 75 (3%) developed neoplasms. In conclusion, patients with the RAF1:c.770C > T pathogenic variant show a particularly severe phenotype characterized by rapidly progressive neonatal HCM and high mortality rate suggesting the necessity of careful monitoring and early intervention to prevent or slow down the progression of HCM.

Aberrant connectivity in the hippocampus, bilateral insula and temporal poles precedes treatment resistance in first-episode psychosis: a prospective resting-state functional magnetic resonance imaging study with connectivity concordance mapping.

Functional connectivity resting-state functional magnetic resonance imaging has been proposed to predict antipsychotic treatment response in schizophrenia. However, only a few prospective studies have examined baseline resting-state functional magnetic resonance imaging data in drug-naïve first-episode schizophrenia patients with regard to subsequent treatment response. Data-driven approaches to conceptualize and measure functional connectivity patterns vary broadly, and model-free, voxel-wise, whole-brain analysis techniques are scarce. Here, we apply such a method, called connectivity concordance mapping to resting-state functional magnetic resonance imaging data acquired from an Asian sample (n = 60) with first-episode psychosis, prior to pharmaceutical treatment. Using a longitudinal design, 12 months after the resting-state functional magnetic resonance imaging, we measured and classified patients into two groups based on psychometric testing: treatment responsive and treatment resistant. Next, we compared the two groups' connectivity concordance maps that were derived from the resting-state functional magnetic resonance imaging data at baseline. We have identified consistently higher functional connectivity in the treatment-resistant group in a network including the left hippocampus, bilateral insula and temporal poles. These data-driven novel findings can help researchers to consider new regions of interest and facilitate biomarker development in order to identify treatment-resistant schizophrenia patients early, in advance of treatment and at the time of their first psychotic episode.

Identification of the needs and priorities of older people and stakeholders in rural and urban areas of Santo Andre, Brazil.

BACKGROUND: There are few data reporting the needs and priorities of older adults in Brazil. This hampers the development and/or implementation of policies aimed at older adults to help them age well. The aim of this study was to understand areas of importance, priorities, enablers and obstacles to healthy ageing as identified by older adults and key stakeholders in both urban and rural environments. METHODS: Two locations were selected, one urban and one rural in the municipality of Santo André, in the metropolitan region of São Paulo (SP). Workshops for older adults (>60 y) and stakeholders were conducted separately in each location. The workshops incorporated an iterative process of discussion, prioritisation and ranking of responses, in roundtable groups and in plenary. Areas of commonality and differences between older adult and stakeholder responses were identified by comparing responses between groups as well as mapping obstacles and enablers to healthy ageing identified by older adults, to the priorities identified by stakeholder groups. The socio-ecologic model was used to categorise responses. RESULTS: There were few shared responses between stakeholders and older adults and little overlap between the top ranked responses of urban and rural groups. With respect to areas of importance, both stakeholder groups ranked policies for older people within their top five reponses. Both older adult groups ranked keeping physically and mentally active, and nurturing spirituality. There was a marked lack of congruence between older adults' obstacles and enablers to healthy ageing and stakeholder priorities, in both urban and rural settings. Most responses were located within the Society domain of the socio-ecologic model, although older adults also responded within the Individual/ Relationships domains, particularly in ranking areas of most importance for healthy ageing. CONCLUSIONS: Our results highlight substantial differences between older adults and stakeholders with respect to areas of importance, priorities, enablers and obstacles to healthy ageing, and point to the need for more engagement between those in advocacy and policymaking roles and the older people whose needs they serve.

Assessment of gene-disease associations and recommendations for genetic testing for somatic variants in vascular anomalies by VASCERN-VASCA.

BACKGROUND: Vascular anomalies caused by somatic (postzygotic) variants are clinically and genetically heterogeneous diseases with overlapping or distinct entities. The genetic knowledge in this field is rapidly growing, and genetic testing is now part of the diagnostic workup alongside the clinical, radiological and histopathological data. Nonetheless, access to genetic testing is still limited, and there is significant heterogeneity across the approaches used by the diagnostic laboratories, with direct consequences on test sensitivity and accuracy. The clinical utility of genetic testing is expected to increase progressively with improved theragnostics, which will be based on information about the efficacy and safety of the emerging drugs and future molecules. The aim of this study was to make recommendations for optimising and guiding the diagnostic genetic testing for somatic variants in patients with vascular malformations. RESULTS: Physicians and lab specialists from 11 multidisciplinary European centres for vascular anomalies reviewed the genes identified to date as being involved in non-hereditary vascular malformations, evaluated gene-disease associations, and made recommendations about the technical aspects for identification of low-level mosaicism and variant interpretation. A core list of 24 genes were selected based on the current practices in the participating laboratories, the ISSVA classification and the literature. In total 45 gene-phenotype associations were evaluated: 16 were considered definitive, 16 strong, 3 moderate, 7 limited and 3 with no evidence. CONCLUSIONS: This work provides a detailed evidence-based view of the gene-disease associations in the field of vascular malformations caused by somatic variants. Knowing both the gene-phenotype relationships and the strength of the associations greatly help laboratories in data interpretation and eventually in the clinical diagnosis. This study reflects the state of knowledge as of mid-2023 and will be regularly updated on the VASCERN-VASCA website (VASCERN-VASCA, https://vascern.eu/groupe/vascular-anomalies/ ).

Genome-wide CRISPR screens identify the YAP/TEAD axis as a driver of persister cells in EGFR mutant lung cancer.

Most lung cancer patients with metastatic cancer eventually relapse with drug-resistant disease following treatment and EGFR mutant lung cancer is no exception. Genome-wide CRISPR screens, to either knock out or overexpress all protein-coding genes in cancer cell lines, revealed the landscape of pathways that cause resistance to the EGFR inhibitors osimertinib or gefitinib in EGFR mutant lung cancer. Among the most recurrent resistance genes were those that regulate the Hippo pathway. Following osimertinib treatment a subpopulation of cancer cells are able to survive and over time develop stable resistance. These 'persister' cells can exploit non-genetic (transcriptional) programs that enable cancer cells to survive drug treatment. Using genetic and pharmacologic tools we identified Hippo signalling as an important non-genetic mechanism of cell survival following osimertinib treatment. Further, we show that combinatorial targeting of the Hippo pathway and EGFR is highly effective in EGFR mutant lung cancer cells and patient-derived organoids, suggesting a new therapeutic strategy for EGFR mutant lung cancer patients.

Enteral nutrition: An underappreciated source of patient safety events.

Enteral nutrition (EN) therapies are prescribed for patients not able to maintain adequate nutrition through the oral route. Medical errors and close calls associated with the provision of EN therapy leading to actual and potential patient harm have been reported. The purpose of this study was to determine the number, type, and severity of safety events related to the provision of EN therapies reported to a national database and provide workable recommendations from the literature to improve safety. An interdisciplinary team queried the National Center for Patient Safety (NCPS) Joint Patient Safety Reporting (JPSR) system using keywords related to EN therapy use. The team reviewed the number, type, and severity of reported events and safety codes as categorized by the NCPS and then thematically classified the narratives using the Medication Use Process (MUP). Our query revealed 1227 safety events related to the EN keywords. Thematic analysis of the top five event subtypes (n = 1030) revealed that there were 691 EN safety reports directly related to an MUP step, and the majority fell into the steps of administering (31%), followed by monitoring (28%), dispensing (26%), prescribing (11%), and transcription (4%), with many events involving more than one MUP step. Safety events associated with the provision of EN therapies leading to patient harm have been reported to the JPSR system. To improve safety related to EN use, modifications to prescribing, transcribing/documenting, dispensing, administering, and monitoring of prescribed EN therapies are needed.

Testing a health baseline during a bivalve mollusc mortality event: An investigation into die-offs of pipi Paphies australis from Aotearoa New Zealand.

Disease is a major threat to the economic, ecological and cultural services provided by wild bivalve populations. Over the past decade anecdotal reports on declining health of native bivalve populations around Aotearoa New Zealand have been supported by increasing observations of mass die-offs. Causes of declining health and mass die-offs of wild bivalves are not clear and could be due to a number of interactive and cumulative factors, including declining water quality, climate change, or disease. Pipi/kokota (Paphies australis) within the Whangarei area (northern New Zealand) have suffered repeated die-offs and declining health since at least 2009. Baseline health data for wild native bivalve populations are scarce making it difficult to identify changes in pathogen infection prevalence and intensity and infer their importance to host health. This research aimed to examine and document the health of pipi in Whangarei with the objective of identifying factors that may contribute to their ill health and lack of population recovery. We sampled pipi from four sites within Whangarei, eight times across two years (total n = 640) to establish a health baseline using histopathology, general bacteriology, and qPCR for the intracellular bacteria Endozoicomonas spp. Three pipi mass die-offs occurred during the sampling window that were opportunistically sampled to compare against the health baseline established using healthy pipi. An increase in bacterial growth and a decrease in the abundance of Endozoicomonas spp. in mortality pipi was observed compared with the health baseline. Establishing a health baseline for pipi from Whangarei provided a benchmark to assess changes in a pipi population experiencing high mortality. Such data can help identify factors contributing to die-offs and to help inform what mitigation, if any, is possible in wild shellfish populations.

Priorities and barriers for ageing well; results from stakeholder workshops in rural and urban Rwanda.

BACKGROUND: The National Older Person's Policy of 2021 in Rwanda highlights the need for social protection of older populations. However, there is a lack of local knowledge regarding the priorities and challenges to healthy aging faced by older people and their caregivers. OBJECTIVES: This study aimed to identify and compare the needs and priorities of older people and other stakeholders involved in caring for them in rural and urban areas of Rwanda. METHODS: The study was conducted in two locations, Kigali (urban) and Burera district (rural). Each site hosted two separate one-day workshops with older people (≥60 years) and stakeholders (all ages). Discussions were held in plenary and roundtable-groups to generate a list of the top 4 prioritized responses on areas of importance, priorities/enablers to be addressed, and obstacles to living a healthy and active life for older people. The research team identified similarities between stakeholder and older people's responses in each area and a socio-ecological model was used to categorize findings. RESULTS: There were substantial differences in responses between rural and urban areas and between older people and stakeholders. For each question posed, in each rural or urban area, there was only agreement between stakeholders and older people for a maximum of one response. Whereas, when comparing responses from the same participant groups in urban or rural settings, there was a maximum agreement of two responses, with two questions having no agreement in responses at all. Responses across all discussion-areas were mostly categorized within the Societal level, with Individual, Relationship, and Environment featuring less frequently. CONCLUSION: This study highlights the need for contextually curated interventions to address the concerns of older adults and their caregivers in rural and urban settings. An inclusive and multidimensional approach is needed to conquer the barriers that impede healthy aging, with input from various stakeholders.

DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism.

Autosomal dominant Kabuki syndrome (KS) is a rare multiple congenital anomalies/neurodevelopmental disorder caused by heterozygous inactivating variants or structural rearrangements of the lysine-specific methyltransferase 2D (KMT2D) gene. While it is often recognizable due to a distinctive gestalt, the disorder is clinically variable, and a phenotypic scoring system has been introduced to help clinicians to reach a clinical diagnosis. The phenotype, however, can be less pronounced in some patients, including those carrying postzygotic mutations. The full spectrum of pathogenic variation in KMT2D has not fully been characterized, which may hamper the clinical classification of a portion of these variants. DNA methylation (DNAm) profiling has successfully been used as a tool to classify variants in genes associated with several neurodevelopmental disorders, including KS. In this work, we applied a KS-specific DNAm signature in a cohort of 13 individuals with KMT2D VUS and clinical features suggestive or overlapping with KS. We succeeded in correctly classifying all the tested individuals, confirming diagnosis for three subjects and rejecting the pathogenic role of 10 VUS in the context of KS. In the latter group, exome sequencing allowed to identify the genetic cause underlying the disorder in three subjects. By testing five individuals with postzygotic pathogenic KMT2D variants, we also provide evidence that DNAm profiling has power to recognize pathogenic variants at different levels of mosaicism, identifying 15% as the minimum threshold for which DNAm profiling can be applied as an informative diagnostic tool in KS mosaics.

Congenital Heart Defects in Patients with Molecularly Confirmed Sotos Syndrome.

Sotos syndrome is an autosomal dominant condition characterized by overgrowth with advanced bone age, macrodolicocephaly, motor developmental delays and learning difficulties, and characteristic facial features caused by heterozygous pathogenetic variants in the NSD1 gene located on chromosome 5q35. The prevalence of heart defects (HDs) in individuals with Sotos syndrome is estimated to be around 15-40%. Septal defects and patent ductus arteriosus are the most commonly diagnosed malformations, but complex defects have also been reported. The aim of our study was to analyze the prevalence of HD, the anatomic types, and the genetic characteristics of 45 patients with Sotos syndrome carrying pathogenetic variants of NSD1 or a 5q35 deletion encompassing NSD1, who were followed at Bambino Gesù Children's Hospital in Rome. Thirty-nine of the forty-five patients (86.7%) had a mutation in NSD1, while six of the forty-five (13.3%) had a deletion. Most of the patients (62.2%, 28/45) were male, with a mean age of 14 ± 7 years (range 0.2-37 years). A total of 27/45 (60.0%) of the patients had heart defects, isolated or combined with other defects, including septal defects (12 patients), aortic anomalies (9 patients), mitral valve and/or tricuspid valve dysplasia/insufficiency (1 patient), patent ductus arteriosus (3 patients), left ventricular non-compaction/hypertrabeculated left ventricle (LV) (4 patients), aortic coarctation (1 patient), aortopulmonary window (1 patient), and pulmonary valve anomalies (3 patients). The prevalences of HD in the two subgroups (deletion versus intragenic mutation) were similar (66.7% (4/6) in the deletion group versus 58.91% (23/39) in the intragenic variant group). Our results showed a higher prevalence of HD in patients with Sotos syndrome in comparison to that described in the literature, with similar distributions of patients with mutated and deleted genes. An accurate and detailed echocardiogram should be performed in patients with Sotos syndrome at diagnosis, and a specific cardiological follow-up program is needed.

Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions.

Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62 Mb minimal critical region at 20q11.2, encompassing three genes GDF5, EPB41L1, and SAMHD1, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359 kb at 20q11.2, containing six MIM genes, including two disease-causing genes, GDF5 and CEP250. The second critical region spans 706 kb at 20q12, encompassing four MIM genes, including two disease-causing genes, MAFB and TOP1. We propose GDF5 to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize TOP1 as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.

Corrigendum: PTCHD1 gene mutation/deletion: the cognitive-behavioral phenotyping of four case reports.

[This corrects the article DOI: 10.3389/fpsyt.2023.1327802.].