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Abstract Background Schistosomiasis remains a public health concern worldwide. It is responsible for more than 240 million cases in 78 countries, 40 million of whom are women of childbearing age. In the Senegal River basin, both Schistosoma haematobium and Schistosoma mansoni are very prevalent in school-age children. However, there is a lack of information on the burden of schistosomiasis in pregnant women, which can cause complications in the pregnancy outcome. This study aimed to determine the prevalence and associated factors of schistosomiasis in pregnant women. Methods We conducted a prospective cross-sectional study of pregnant women attending antenatal clinics at the health center of the Senegalese Sugar Company and at the hospital of Richard Toll between August and December 2021. The urine and stool samples collected were examined using microscopy techniques and quantitative polymerase chain reaction (qPCR) to detect the presence of S. haematobium and S. mansoni. The urines were previously tested using urine reagent strips to detect hematuria and proteinuria. Socio-demographical, clinical, and diagnostically data were recorded by the midwife and the gynaecologist. The data were analyzed using a logistic regression model. Results Among the 298 women examined for the infection by microscopic, 65 (21.81%) were infected with urogenital schistosomiasis, 10 (3.36%) with intestinal schistosomiasis, and 4 (1.34%) were co-infected with both types of schistosomiasis. Out of the 288 samples tested by qPCR, 146 (48.99%) were positive for S. haematobium, 49 (35.51%) for S. mansoni and 22 (15.94%) for both species (co-infection). Pregnant women having microscopic haematuria and proteinuria were significantly more infected (p

Abstract Background Digital health is being used as an accelerator to improve the traditional healthcare system, aiding countries in achieving their sustainable development goals. Burkina Faso aims to harmonize its digital health interventions to guide its digital health strategy for the coming years. The current assessment represents upstream work to steer the development of this strategic plan. Methods This was a quantitative, descriptive study conducted between September 2022 and April 2023. It involved a two-part survey: a self-administered questionnaire distributed to healthcare information managers in facilities, and direct interviews conducted with software developers. This was complemented by a documentary review of the country’s strategic and standards documents on digital transformation. Results Burkina Faso possesses a relatively comprehensive collection of governance documents pertaining to digital transformation. The study identified a total of 35 digital health interventions. Analysis showed that 89% of funding originated from technical and financial partners as well as the private sector. While the use of open-source technologies for the development of the applications, software, or platforms used to implement these digital health interventions is well established (77%), there remains a deficiency in the integration of data from different platforms. Furthermore, the classification of digital health interventions revealed an uneven distribution between the different elements across domains: the health system, the classification of digital health interventions (DHI), and the subsystems of the National Health Information System (NHIS). Most digital health intervention projects are still in the pilot phase (66%), with isolated electronic patient record initiatives remaining incomplete. Within the public sector, these records typically take the form of electronic registers or isolated specialty records in a hospital. Within the private sector, tool implementation varies based on expressed needs. Challenges persist in adhering to interoperability norms and standards during tool design, with minimal utilization of the data generated by the implemented tools. Conclusion This study provides an insightful overview of the digital health environment in Burkina Faso and highlights significant challenges regarding intervention strategies. The findings serve as a foundational resource for developing the digital health strategic plan. By addressing the identified shortcomings, this plan will provide a framework for guiding future digital health initiatives effectively.

Abstract Background Mitral valve prolapse (MVP) is a common heart disorder characterized by an excessive production of proteoglycans and extracellular matrix in mitral valve leaflets. Large-scale genome-wide association study (GWAS) underlined that MVP is heritable. The molecular underpinnings of the disease remain largely unknown. Methods We interrogated cross-modality data totaling more than 500,000 subjects including GWAS, 4809 molecules of the blood proteome, and genome-wide expression of mitral valves to identify candidate drivers of MVP. Data were investigated through Mendelian randomization, network analysis, ligand-receptor inference and digital cell quantification. Results In this study, Mendelian randomization identify that 33 blood proteins, enriched in networks for immunity, are associated with the risk of MVP. MVP- associated blood proteins are enriched in ligands for which their cognate receptors are differentially expressed in mitral valve leaflets during MVP and enriched in cardiac endothelial cells and macrophages. MVP-associated blood proteins are involved in the renewal-polarization of macrophages and regulation of adaptive immune response. Cytokine activity profiling and digital cell quantification show in MVP a shift toward cytokine signature promoting M2 macrophage polarization. Assessment of druggability identify CSF1R, CX3CR1, CCR6, IL33, MMP8, ENPEP and angiotensin receptors as actionable targets in MVP. Conclusions Hence, integrative analysis identifies networks of candidate molecules and cells involved in immune control and remodeling of the extracellular matrix, which drive the risk of MVP.

Abstract Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.

ABSTRACT As climate change alters Earth’s biomes, it is expected the transmission dynamics of mosquito-borne viruses will change. While the effects of temperature changes on mosquito-virus interactions and the spread of the pathogens have been elucidated over the last decade, the impact of relative humidity changes is still relatively unknown. To overcome this knowledge gap, we exposed Aedes aegypti females to various humidity conditions. We measured different components of vectorial capacity such as survival, blood-feeding rates, and changes in infection and dissemination of Zika virus. Survival decreased as the humidity level decreased, while infection rates increased as the humidity level decreased. Alternatively, blood feeding rates and disseminated infection rates peaked at the intermediate 50% relative humidity treatment but were the same in the 30% and 80% relative humidity treatments. These results provide empirical evidence that Ae. aegypti exposure to low humidity can enhance Zika virus infection in the mosquito, which has important implications in predicting how climate change will impact mosquito-borne viruses.IMPORTANCEViruses transmitted by mosquitoes to humans are a major public health burden and are expected to increase under climate change. While we know that temperature is an important driver of variation in arbovirus replication in the mosquito, very little is known about how other relevant climate variables such as humidity will influence the interaction between mosquitoes and the viruses they transmit. Given the variability in humidity across environments, and the predicted changes in humidity under climate change, it is imperative that we also study the impact that it has on mosquito infection and transmission of arboviruses.

We conducted a cross-sectional serosurvey for chikungunya virus (CHIKV) exposure in fruit bats in Senegal during 2020–2023. We found that 13.3% (89/671) of bats had CHIKV IgG; highest prevalence was in Eidolon helvum (18.3%, 15/82) and Epomophorus gambianus (13.7%, 63/461) bats. Our results suggest these bats are naturally exposed to CHIKV.

Abstract Alterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processes in utero. A frequently identified mode of action for this interaction is the induction of hepatic detoxification mechanisms (e.g. SULTs and UGTs), which lead to TH conjugation and elimination and therefore interfere with hormonal homeostasis, fulfilling the endocrine disruptors (EDs) definition. A short-term study in rats with dietary exposure to cyproconazole, epoxiconazole and prochloraz was conducted and hepatocyte hypertrophy, hepatic UGT activity and Phase 1/2 gene expression inductions were observed together with changes in TH levels and thyroid follicular hypertrophy and hyperplasia. To test for specific interaction with the thyroid hormone system, in vitro assays were conducted covering thyroidal I-uptake (NIS), TH transmembranal transport via MCT8 and thyroid peroxidase (TPO) function. Assays for iodothyronine deiodinases (DIO1–DIO3) and iodotyrosine deiodinase (DEHAL1) were included, and from the animal experiment, Dio1 and Dehal1 activities were measured in kidney and liver as relevant local indicators and endpoints. The fungicides did not affect any TH-specific KEs, in vitro and in vivo, thereby suggesting hepatic conjugation as the dominant MoA.

Abstract Assembled genome sequences are being generated at an exponential rate. Here we present FCS-GX, part of NCBI’s Foreign Contamination Screen (FCS) tool suite, optimized to identify and remove contaminant sequences in new genomes. FCS-GX screens most genomes in 0.1–10 min. Testing FCS-GX on artificially fragmented genomes demonstrates high sensitivity and specificity for diverse contaminant species. We used FCS-GX to screen 1.6 million GenBank assemblies and identified 36.8 Gbp of contamination, comprising 0.16% of total bases, with half from 161 assemblies. We updated assemblies in NCBI RefSeq to reduce detected contamination to 0.01% of bases. FCS-GX is available at https://github.com/ncbi/fcs/ or https://doi.org/10.5281/zenodo.10651084 .

The reaction of the Schiff base 2-[1-(pyridin-2-yl)ethylideneamino]ethanol (HL), which is formed by reaction of 2-aminoethanol and 2-acetylpyridine with CuBr2 in ethanol results in the isolation of the new polymeric complex poly[hexa-μ-bromido-bis{2-[1-(pyridin-2-yl)ethylideneamino]ethanolato}tetracopper(II)], [Cu4Br6(C9H11N2O)2]n or [Cu4Br6L2]n. The asymmetric unit of the crystal structure of the polymeric [Cu4Br6L2]n complex is composed by four copper (II) cations, two monodeprotonated molecules of the ligand, and six bromide anions, which act as bridges. The ligand molecules act in a tridentate fashion through their azomethine nitrogen atoms, their pyridine nitrogen atoms, and their alcoholate O atoms. The crystal structure shows two types of geometries in the coordination polyhedrons around Cu2+ ions. Two copper cations are situated in a square-based pyramidal environment, while the two other copper cations adopt a tetrahedral geometry. Bromides anions acting as bridges between two metal ions connect the units, resulting in a tetranuclear polymer compound.

Coumarins have demonstrated a broad spectrum of pharmacological activities, including significant anticancer properties. Recently, a series of cyclocoumarol derivatives, a pyranocoumarin known for its anticoagulant and anti-inflammatory effects, have been synthesized and shown to have a selective inhibitory effect on cyclooxygenase-2 (COX-2). In this study, we evaluated the anticancer effects of these cyclocoumarol derivatives for the first time. We tested their antiproliferative effects on several human cancer cell lines, including MDAMB231, A549, MCF7, SF268, HCT116, HeLa, and Jurkat. The MTT assay revealed that the methylated cyclocoumarol derivative, 2-methoxy-2-methyl-(1-(p-tolyl))-3,4-dihydropyrano [3,2-c] chromen-5(2H)-one, 5b exhibited the most potent antiproliferative activity, particularly against MDAMB231 cells. Further investigations demonstrated that 5b induced apoptosis in MDAMB231 cells via the mitochondrial pathway, as indicated by increased Bax and decreased Bcl2 levels, along with caspase-3 activation and PARP cleavage. Additionally, compound 5b significantly inhibited the clonogenic potential of MCF7 cells and reduced the migration capacity of MDAMB231, SF268, and A549 cells. These findings suggest that 5b is a promising lead compound for developing new anticancer agents, with the potential for chemical optimization to enhance its efficacy.

The second edition of the Conference on Economic and Monetary Sovereignty of Africa was held in Dakar, Senegal, on October 25–28, 2022. Participants from around the world debated the theme “Facing the Socio-Ecological Crisis: Delinking and the Question of Global Reparations.” The event was designed as a follow-up on discussions begun during the first edition (held in Tunis in 2019; see Ben Gadha et al. 2021), as well as an opportunity to reflect on recent developments.  The Dakar Declaration is one of the main byproducts of four days of intense, fruitful, and comradely debates on the triptych of delinking, socio-ecological resilience, and reparations. It is an internationalist manifesto and a global action plan.

Objectif : La transmission mère-enfant du VIH durant l’allaitement est un problème de santé publique. Le but de cette étude était d’évaluer l’intérêt du suivi thérapeutique pharmacologique des femmes allaitantes sous ARV et leurs enfants à Bamako. Méthodes : Les patientes ont été recrutées du 1er septembre 2015 au 30 septembre 2016 suite à l’obtention de leur consentement éclairé. Les mères et leur enfant ont été suivis dans le service de pédiatrie du CHU Gabriel Touré. Les charges virales plasmatiques ont été réalisées à l’UCRC de Bamako. La détermination des concentrations plasmatiques des médicaments a été réalisée au laboratoire de Pharmacocinétique de Toulouse. Les données ont été saisies et analysées sur le logiciel SPSS version 20. Résultats : L’âge moyen des mères était de 29ans±75 [19-41ans]. A J0, une seule des patientes avait une charge virale plasmatique détectable soit 3,33%(6610copies/ml) et 73,91% des mères avaient un taux de CD4 supérieur à350cellules/mm3. Après 6mois, nous avions trouvé 3 mères qui avaient une charge virale détectable (200copies/ml ; 72copies/ml et 4777 copies/ml) et 86,36% des mères avaient un taux de CD4 supérieur à350cellules/mm3. Les concentrations plasmatiques médianes mères du lopinavir, de l’efavirenz à 3 mois étaient respectivement de 5770ng/ml ; 3505ng/ml et à 6 mois de 5850ng/ml ; 3245ng/ml. Tous les nourrissons avaient une PCR négative à 3 mois et 6 mois de suivi. Conclusion : La mesure des paramètres biologiques constitue un maillon essentiel dans la prise en charge des femmes allaitantes VIH positif au Mali.

Yaws, caused by Treponema pallidum ssp. pertenue, remains a significant public health concern in tropical regions of West Africa and the South Pacific, primarily affecting children in remote areas with limited access to hygiene and sanitation. In this study, conducted in three endemic countries of West Africa where yaws remains a significant public health concern (Ghana, Cameroon, and Côte d'Ivoire), we aimed to assess the knowledge, attitudes, and practices related to yaws among community members, community health workers (CHWs), and traditional healers. The study revealed variations in the perception of causes of yaws among community members: the majority or participants in Ghana attributed yaws to germs (60.2%); in Cameroon the most reported form of transmission was contact with or drinking infected water sources (44.6%); and in Côte d'Ivoire both of these answers were also the most prevalent (60.3% germs and 93.% water sources). A substantial proportion of participants in Côte d'Ivoire also associated yaws with witchcraft and divine punishment (44.8%). Only a small proportion of individuals in Ghana and Côte d'Ivoire correctly identified contact with an infected person as a form of transmission (11.9% and 20.7%, respectively) and less than half in Cameroon (42.6%), although more than 98% of all participants reported avoidance behaviours towards yaws infected people due to fear of getting infected. Most participants expressed a preference for seeking care at hospitals (49.2%, 60.6%, 86.2%) or health care professionals including doctors and nurses (58.5%, 41,5% and 17.2%) if they were diagnosed with yaws, although a quarter of participants in Côte d'Ivoire also sought support from traditional healers. The CHWs interviewed were generally well-trained on yaws causes and treatment options, although they often reported low availability of treatment and diagnostic tests for yaws. Our findings underscore the need for community education, awareness campaigns, ongoing CHW training, and improved access to yaws treatment and diagnostic resources. The data also suggest that collaboration with traditional healers, who usually hold a highly esteemed position in the society, such as giving training on yaws causes and transmission or exchanging knowledge on treatment options, could be beneficial in certain regions, particularly in Côte d'Ivoire.

Sorghum and pearl millet have adapted to the socioecological environment in the dryland of West Africa and have been the staple crops for many years. Engaging key stakeholders and improving the sorghum and pearl millet breeding process is essential to addressing the evolving demands of end-users and environmental conditions. Unlike most trait preference studies focusing on men and women farmers’ trait choices, we examined sorghum and pearl millet key value chain actors (VCA), including producers, processors, traders, and consumers. We identified their preferred traits of varieties that need to be mainstreamed into the breeding pipelines. Drawing on the past efforts and experiences of the sorghum and pearl millet breeding programs from the last 30 years, the study was designed to integrate gender equality in sorghum and pearl millet breeding decisions and traits prioritization in West Africa. This process was implemented in phases, leading to the drafting of gender-responsive and client-oriented product profiles. The paper elicited an understanding of how the roles and interests of sorghum and pearl millet VCA influence their varietal choice and adoption decisions. The study found both differences and similarities in the trait preferences of the men and women VCA. Most women, mainly in the production and processing nodes, prefer varieties with specific food and grain quality traits, while men prioritize grain yield and biotic stress resistance traits. Even though both men’s and women’s varietal choices align with their roles in production and consumption, grain yield was commonly desired across gender, crop, and value chain segments. The findings revealed that the gendered interest of actors in the crops’ value chain determines their choice of variety. Gender responsiveness requires identifying and understanding the needs and choices of the sorghum and millet VCA and mainstreaming these into the breeding pipeline. The approach employed in the study elicits the understanding, roles, and interests of the various actors and how these factors influence men’s and women’s decisions to adopt a crop variety. All major stakeholders should co-develop product profiles for the variety being developed to enable co-ownership, increase adoption, and improve gender equity in agricultural technology development and deployment.

Purpose: To report a novel case of Urrets-Zavalia syndrome (UZS). Observation: A 59-year-old man underwent removal of a dislocated intraocular lens and placement of a scleral-sutured intraocular lens. After surgery, the pupil in the operative eye was dilated, fixed, and unresponsive to constricting drops. Conclusion: This case expands the known etiology of UZS. Possible preventative measures may include pre-operative screening for plateau iris and intra-operative use of iris hooks instead of pharmacological dilation.

Improving sorghum adoption rates by developing adapted varieties that meet end-user preferences is a major challenge in West Africa. In this study, a participatory rural appraisal was undertaken to identify the main sorghum production constraints, farmers’ preferred variety traits and their perceptions on sorghum grain mold. The study was conducted in four representative rural communities located in the main sorghum producing area of Senegal. A total of 260 farmers were interviewed and data were collected through focus group discussions and individual questionnaires. Our results indicated that Striga, insects, poor soil fertility and drought are the major sorghum producing constraints in Senegal. Grain mold was identified as the second most important sorghum disease after the damping-off. Discoloration on grain surface was the most important criteria farmers used to recognize the disease. The most important sorghum traits farmers desired in improved varieties are medium to short plant maturity cycle, medium plant height, large open or semi-compact panicle, big and white grain, and adaptation to local growing conditions. The results showed that the sorghum cropping system is dominated by male farmers who mainly grow local landraces. These results will provide updated recommendations for the breeding products profile to meet end-user preferences in Senegal.

Abstract Background Ultra-processed foods (UPF), as proposed by the Nova food classification system, are linked to the development of obesity and several non-communicable chronic diseases and deaths from all causes. The Nova-UPF screener developed in Brazil is a simple and quick tool to assess and monitor the consumption of these food products. The aim of this study was to adapt and validate, against the 24-hour dietary recall, this short food-based screener to assess UPF consumption in the Senegalese context. Methods The tool adaptation was undertaken using DELPHI methodology with national experts and data from a food market survey. Following the adaptation, sub-categories were renamed, restructured and new ones introduced. The validation study was conducted in the urban area of Dakar in a convenience sample of 301 adults, using as a reference the dietary share of UPF on the day prior to the survey, expressed as a percentage of total energy intake obtained via 24-hour recall. Association between the Nova-UPF score and the dietary share of UPF was evaluated using linear regression models. The Pabak index was used to assess the agreement in participants’ classification according to quintiles of Nova-UPF score and quintiles of the dietary share of UPF. Results The results show a linear and positive association (p-value

This work addresses the problem of supervised classification for highly correlated high-dimensional data describing non-independent observations to identify SNPs related to a phenotype. We use a general penalized linear mixed model with a single random effect that performs simultaneous SNP selection and population structure adjustment in high-dimensional prediction models. Specifically, the model simultaneously selects variables and estimates their effects, taking into account correlations between individuals.Single nucleotide polymorphisms (SNPs) are a type of genetic variation and each SNP represents a difference in a single DNA building block, namely a nucleotide. Previous research has shown that SNPs can be used to identify the correct source population of an individual and can act in isolation or simultaneously to impact a phenotype. In this regard, the study of the contribution of genetics in infectious disease phenotypes is of great importance.In this study, we used uncorrelated variables from the construction of blocks of correlated variables done in a previous work to describe the most related observations of the dataset. The model was trained with 90% of the observations and tested with the remaining 10%. The best model obtained with the generalized information criterion (GIC) identified the SNP named rs2493311 located on the first chromosome of the gene called PRDM16 ((PR/SET domain 16)) as the most decisive factor in malaria attacks.

Abstract Background Over the past two decades, preventive chemotherapy (PC) with praziquantel (PZQ) is the major strategy for controlling schistosomiasis in Senegal. The objective of this analysis was to update the endemicity of schistosomiasis at community level for better targeting mass treatment with PZQ in Senegal. Methods Demographic and epidemiological data from 1610 community health areas were analyzed using the schistosomiasis community data analysis tool of Expanded Special Project for Elimination of Neglected Tropical Diseases which developed by World Health Organization/Africa Office (WHO/AFRO). The tool uses a WHO/AFRO decision tree for areas without epidemiological data to determine whether mass treatment should be continued at community level. Descriptive analysis was performed. Results Overall, the endemicity of 1610 community health areas were updated based on the data from the district endemicity (33.5%) and the form of Join request for selected PC medicine (40.5%). Up to 282 (17.5%) and 398 (24.7%) of community health areas were classified as moderate and high endemicity. 41.1% of communities were non endemic. High endemicity was more important in Tambacounda, Saint Louis, Matam, Louga and Kedougou. A change in endemicity category was observed when data was disagregted from district level to community level. Implementation units classified non endemic were more important at community level (n = 666) compared to district level (n = 324). Among 540 areas previously classified high endemic at district level, 392 (72.6%) remained high prevalence category, while 92 (17.0%) became moderate, 43 (8.0%) low and 13 (2.4%) non-endemics at community level. Number of implementation units requiring PC was more important at district level (1286) compared to community level (944). Number of school aged children requiring treatment was also more important at district level compared to community level. Conclusions The analysis to disaggregate data from district level to community level using the WHO/AFRO schistosomiasis sub-district data optimization tool provide an update of schistosomiasis endemicity at community level. This study has allowed to better target schistosomiasis interventions, optimize use of available PZQ and exposed data gaps.

We present a laser–plasma electron accelerator module designed to be driven by high-repetition-rate lasers for industrial applications of laser-driven electron beams. It consists of a single vacuum chamber containing all the necessary components for producing, optimizing, and monitoring electron beams generated via laser wakefield acceleration in a gas jet when driven by a suitable laser. The core methods in this paper involve a comprehensive metrological assessment of the driving laser by rigorous temporal laser pulse characterization and contrast measurements, supplemented by detailed spatiotemporal distribution analyses of the laser focus. Results demonstrate the good stability and reproducibility of the laser system, confirming its suitability for advanced scientific and industrial applications. We further demonstrate the functionality of the laser–plasma accelerator module diagnostics, perform target density characterizations, and time-resolved laser–plasma shadowgraphy. Current limitations of the set-up preventing first electron acceleration are analyzed and an outlook for future experiments is given. Our work is a first step towards the wide dissemination of fully integrated laser–plasma accelerator technology.

Albinism is a genetically heterogeneous disease in which 21 genes are known so far. Its inheritance mode is autosomal recessive except for one X-linked form. The molecular analysis of exonic sequences of these genes allows for about a 70% diagnostic rate. About half (15%) of the unsolved cases are heterozygous for one pathogenic or probably pathogenic variant. Assuming that the missing variant may be located in non-coding regions, we performed sequencing for 122 such heterozygous patients of either the whole genome (27 patients) or our NGS panel (95 patients) that includes, in addition to all exons of the 21 genes, the introns and flanking sequences of five genes, TYR, OCA2, SLC45A2, GPR143 and HPS1. Rare variants (MAF < 0.01) in trans to the first variant were tested by RT-PCR and/or minigene assay. Of the 14 variants tested, nine caused either exon skipping or the inclusion of a pseudoexon, allowing for the diagnosis of 11 patients. This represents 9.8% (12/122) supplementary diagnosis for formerly unsolved patients and 75% (12/16) of those in whom the candidate variant was in trans to the first variant. Of note, one missense variant was demonstrated to cause skipping of the exon in which it is located, thus shedding new light on its pathogenic mechanism. Searching for non-coding variants and testing them for an effect on RNA splicing is warranted in order to increase the diagnostic rate.