Identification of transient receptor potential channel genes from the swimming crab, Portunus Trituberculatus, and their expression profiles under acute temperature stress.

BACKGROUND: Temperature is an important environment factor that is critical to the survival and growth of crustaceans. However, the mechanisms by which crustaceans detect changes in temperature are still unclear. The transient receptor potential (TRP) channels are non-selective cation channels well known for properties in temperature sensation. However, comprehensive understandings on TRP channels as well as their temperature sensing functions are still lacking in crustaceans. RESULTS: In this study, a total of 26 TRP genes were identified in the swimming crab, Portunus trituberculatus, which can be classified into TRPA, TRPC, TRPP, TRPM, TRPML, TRPN and TRPV. Tissue expression analysis revealed a wide distribution of these TRP genes in P. trituberculatus, and antennules, neural tissues, and ovaries were the most commonly expressed tissues. To investigate the responsiveness of TRP genes to the temperature change, 18 TRPs were selected to detect their expression after high and low temperature stress. The results showed that 12 TRPs showed induced gene expression in both high and low temperature groups, while 3 were down-regulated in the low temperature group, and 3 showed no change in expression in either group. CONCLUSIONS: This study characterized the TRP family genes in P. trituberculatus, and explored their involvement in response to temperature stress. Our results will enhance overall understanding of crustacean TRP channels and their possible functions.

Identification of Phytophthora cinnamomi CRN effectors and their roles in manipulating cell death during Persea americana infection.

The oomycete Phytophthora cinnamomi is a devastating plant pathogen with a notably broad host range. It is the causal agent of Phytophthora root rot (PRR), arguably the most economically important yield-limiting disease in Persea americana (avocado). Despite this, our understanding of the mechanisms P. cinnamomi employs to infect and successfully colonize avocado remains limited, particularly regarding the pathogen's ability to maintain its biotrophic and necrotrophic lifestyles during infection. The pathogen utilises a large repertoire of effector proteins which function in facilitating and establishing disease in susceptible host plants. Crinkling and necrosis effectors (CRN/Crinklers) are suspected to manipulate cell death to aid in maintenance of the pathogens biotrophic and necrotrophic lifestyles during different stages of infection. The current study identified 25 P. cinnamomi CRN effectors from the GKB4 genome using an HMM profile and assigned putative function to them as either cell death inducers or suppressors. Function was assigned to 10 PcinCRNs by analysing their RNA-seq expression profiles, relatedness to other functionally characterised Phytophthora CRNs and tertiary protein predictions. The full-length coding sequences for these PcinCRNs were confirmed by Sanger sequencing, six of which were found to have two divergent alleles. The presence of alleles indicates that the proteins encoded may perform contradicting functions in cell death manipulation, or function in different host plant species. Overall, this study provides a foundation for future research on P. cinnamomi infection and cell death manipulation mechanisms.

Genotypic diversity and long-term impact of human bocavirus on diarrheal disease: Insights from historical fecal samples in Brazil.

This study aimed to investigate the frequency and genotypic diversity of human bocavirus (HBoV) in historical fecal samples collected before 2005 in Brazil and understand its natural history in patients with diarrhea. Between 1998 and 2005, 3347 samples were tested for HBoV by RT-PCR, with a detection rate of 5.8% (195/3347). Coinfection with norovirus (NoV) and human adenovirus (HAdV) was found in 34.9% (68/195), indicating HBoV's potential role as a causative agent of diarrheal disease. The detection rate varied over the years (p < 0.05), suggesting natural oscillatory fluctuations. HBoV was more prevalent in fall and winter, with higher positivity in children ≤5 years (p < 0.05), reinforcing that HBoV is an important pathogen in childhood diarrhea. Genotyping (32.8%; 64/195) revealed the circulation of HBoV-1 (79.7%, 51/64), HBoV-3 (12.5%, 8/64), HBoV-2 (6.2%, 4/64), and the rare HBoV-4 (1.6%, 1/64). Difference in HBoV-1 and HBoV-2/-3 mono-infections prevalence (p < 0.05), suggests a potential role of HBoV-1 in the pathogenicity of diarrheal disease. The study highlights HBoV's lasting impact on viral gastroenteritis in Brazil and emphasizes its genotypic diversity. Recommending screening for HBoV in public health laboratories is crucial for understanding its role in gastrointestinal diseases. The data also contribute to understanding the molecular characterization of enteric viruses in historical fecal samples.

Molecular and epidemiological characterization of Staphylococcus aureus causing bovine mastitis in China.

BACKGROUND: Staphylococcus aureus is one of the most prevalent pathogens in bovine mastitis, which leads to substantial financial losses for the dairy industry. RESULTS: In this study, S. aureus (n = 72) was isolated from 18 dairy farms in 15 provinces across China in 2021. The identification of these isolates at the species level was achieved by employing 16S rRNA sequencing. An isothermal amplification method for auxiliary detection of S. aureus was established, which can be employed not only for laboratory detection but also for point-of-care testing (POCT). Molecular characteristics of S. aureus mastitis in Chinese dairy cows were determined through MLST and spa typing. Finally, methicillin-resistant Staphylococcus aureus (MRSA) and MRSA resistance genes were detected using MIC and PCR amplification techniques. 72 isolates were identified as 12 sequence types (STs) and 7 clonal complexes (CC). ST1/CC1 was the dominant prevalent accounting for 33.3 % of the total, and exhibiting a wide distribution range. In terms of spa types, t114 was the dominant type, accounting for 31.9 % of the total, followed by t529 as the second major type. Four S. aureus strains were classified as MRSA according to their levels of oxacillin resistance (MIC ≥4 µg/mL). Among these four MRSA strains, one of them was found to be mecA positive. However, the presence of drug-resistance genes mecA and mecC was not detected in the remaining three MRSA strains, indicating the possible existence of new resistance genes. CONCLUSIONS: Our study investigated the prevalence of S. aureus mastitis in dairy cows in China, while also examined the molecular characteristics and MRSA strains. This information will help with the clinical monitoring, prevention, and control of S. aureus mastitis in dairy cattle.

Optimizing tissue stewardship in non-small cell lung cancer to support molecular characterization and treatment selection: statement from a working group of thoracic pathologists.

Many patients with non-small cell lung cancer do not receive guideline-recommended, biomarker-directed therapy, despite the potential for improved clinical outcomes. Access to timely, accurate, and comprehensive molecular profiling, including targetable protein overexpression, is essential to allow fully informed treatment decisions to be taken. In turn, this requires optimal tissue management to protect and maximize the use of this precious finite resource. Here, a group of leading thoracic pathologists recommend factors to consider for optimal tissue management. Starting from when lung cancer is first suspected, keeping predictive biomarker testing in the front of the mind should drive the development of practices and procedures that conserve tissue appropriately to support molecular characterization and treatment selection.

Characterization of ectomycorrhizal fungal community of Abies Pindrow using sporocarp sampling, morphotyping, and metabarcoding through next-generation sequencing.

Abies pindrow, commonly known as the West-Himalayan Fir, holds great ecological importance as a native tree species in the Himalayas. Beyond its value as a fuel and timber source, it serves as a keystone species within the ecosystem. However, over recent years, extensive degradation and deforestation have afflicted A. pindrow forests. Utilizing ectomycorrhizal fungal symbionts of A. pindrow could prove pivotal in restoring these deteriorated forests. This study aimed to evaluate the diversity and composition of the ectomycorrhizal fungal community associated with A. pindrow. We employed ectomycorrhizal root tip morphotyping, sporocarp sampling, and Illumina MiSeq metabarcoding of the ITS region of fungal nrDNA. The ectomycorrhizal root tips were categorized into 10 morphotypes based on their morphological characteristics, exhibiting an average colonization rate of 74%. Sporocarp sampling revealed 22 species across 10 genera, with Russula being the most prevalent. The metabarcoding yielded 285,148 raw sequences, identifying 326 operational taxonomic units (OTUs) belonging to 193 genera, 114 families, 45 orders, 22 classes, and 6 divisions. Of these, 36 OTUs across 20 genera were ectomycorrhizal, constituting 63.1% of the fungal community. Notably, Tuber was the most abundant, representing 37.42% of the fungal population, followed by Russula at 21.06%. This study provides a comprehensive understanding of mycorrhizal symbionts of A. pindrow. The findings hold significant implications for utilizing dominant ectomycorrhizal fungi in reforestation endeavors aimed at restoring this important Himalayan conifer.

Childhood cancer data initiative: Status report.

In March 2023, over 800 researchers, clinicians, patients, survivors, and advocates from the pediatric oncology community met to discuss the progress of the National Cancer Institute's Childhood Cancer Data Initiative. We present here the status of the initiative's efforts in building its data ecosystem and updates on key programs, especially the Molecular Characterization Initiative and the planned Coordinated National Initiative for Rare Cancers in Children and Young Adults. These activities aim to improve access to childhood cancer data, foster collaborations, facilitate integrative data analysis, and expand access to molecular characterization, ultimately leading to the development of innovative therapeutic approaches.

Molecular characterization, expression analysis and subcellular location of the members of STAT family from spotted seabass (Lateolabrax maculatus).

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a pervasive intracellular signal transduction pathway, involving in biological processes such as cell proliferation, differentiation, apoptosis and immune regulation. In this study, seven STAT genes, STAT1, STAT1-like, STAT2, STAT3, STAT4, STAT5a and STAT5b, were identified and characterized in spotted seabass (Lateolabrax maculatus). Analyses of multiple sequence alignment, genomic organization, phylogeny and conserved synteny were conducted to infer the evolutionary conservation of these genes in the STAT family. The results of the bioinformatics analysis assumed that STAT1 and STAT1-like might be homologous to STAT1a and STAT1b, respectively. Furthermore, the expression of the seven genes were detected in eight tissues of healthy spotted seabass, which revealed that they were expressed in a variety of tissues, mainly in gill, spleen and muscle, and extremely under-expression in liver. The expression of the seven genes in gill, head-kidney, spleen and intestine were significantly induced by lipopolysaccharide (LPS) or Edwardsiella tarda challenge. The expression of most of the LmSTATs were up-regulated, and the highest expression levels at 12 h after LPS stimulation, however, the LmSTATs were down-regulated by E. tarda infection. The results of subcellular localization show that the native LmSTAT1, LmSTAT1-like, LmSTAT2, LmSTAT3 and LmSTAT5a were localized in the cytoplasm, but they were translocated into the nucleus after LPS stimulation. Whereas, LmSTAT4 and LmSTAT5b were translocation into the nucleus whether with LPS stimulation or not. Overall, this is the first study to systematically revealed the localization of STAT members in fish, and indicated that LmSTATs participate in the process of protecting the host from pathogens invasion in the form of entry into nucleus.

Isolation and molecular characterization of lumpy skin disease virus from Tamil Nadu, India during the outbreaks from 2020 to 2022.

Lumpy skin disease (LSD) caused by LSD virus is a WOAH notifiable, high-impact, transboundary poxviral disease of bovines. The first official report of LSDV in India is from Odisha state during August 2019. Since then, cases have been reported from many states including Tamil Nadu, a Southern state of India. The present study deals with isolation and molecular characterization of LSDV from Tamil Nadu during the period August 2020 to July 2022. LSDV was isolated in embryonated chicken eggs (ECE) and BHK 21 cells and was characterized based on P32, RPO30, and GPCR genes. The phylogenetic analysis revealed that Tamil Nadu isolates from India are closely related to other Indian strains, Kenyan strains and strains from neighboring countries such as Bangladesh, Nepal, and Myanmar confirming the common exotic source for the transboundary spread across borders. The presence of unique signature of amino acid (aa) at specific positions (A11, T12, T34, S99, and P199) in the GPCR sequence confirmed the identity of LSDV. A twelve nucleotide (nt94-105) insertion and corresponding aa (TILS) at 30-33 position was found in GPCR sequence and characteristic amino acid proline at 98 position (P98) in the RPO30 gene sequence of our isolates was similar to strains from Bangladesh, Nepal, and Myanmar. Further, dissimilarity of our isolates from Neethling like vaccine strains confirms the circulation of virulent filed strains responsible for the outbreaks.

Hidden Role of Organic Matter in the Immobilization and Transformation of Iodine on Fe-OM Associations.

The biogeochemical processes of iodine are typically coupled with organic matter (OM) and the dynamic transformation of iron (Fe) minerals in aquifer systems, which are further regulated by the association of OM with Fe minerals. However, the roles of OM in the mobility of iodine on Fe-OM associations remain poorly understood. Based on batch adsorption experiments and subsequent solid-phase characterization, we delved into the immobilization and transformation of iodate and iodide on Fe-OM associations with different C/Fe ratios under anaerobic conditions. The results indicated that the Fe-OM associations with a higher C/Fe ratio (=1) exhibited greater capacity for immobilizing iodine (∼60-80% for iodate), which was attributed to the higher affinity of iodine to OM and the significantly decreased extent of Fe(II)-catalyzed transformation caused by associated OM. The organic compounds abundant in oxygen with high unsaturation were more preferentially associated with ferrihydrite than those with poor oxygen and low unsaturation; thus, the associated OM was capable of binding with 28.1-45.4% of reactive iodine. At comparable C/Fe ratios, the mobilization of iodine and aromatic organic compounds was more susceptible in the adsorption complexes compared to the coprecipitates. These new findings contribute to a deeper understanding of iodine cycling that is controlled by Fe-OM associations in anaerobic environments.

Hepatitis E outbreak in the health district of Bocaranga-Koui, Central African Republic, 2018-2019.

BACKGROUND: Hepatitis E virus (HEV) is a major public health disease causing large outbreaks and sporadic cases of acute hepatitis. We investigated an outbreak of HEV infection that occurred in September 2018 in the health district (HD) of Bocaranga-Koui, located in the northwestern part of Central African Republic (CAR). METHODS: Blood samples were collected from 352 patients aged 0-85 years suspected to be infected with yellow fever (YF), according to the World Health Organization YF case definition. The notification forms from recorded cases were used. Water consumed in the HD were also collected. Human samples found negative for anti-YF IgM were then tested by ELISA for anti-HEV IgM and IgG antibodies. Positive anti-HEV (IgM and/or IgG) samples and collected water were then subjected to molecular biology tests using a real time RT-PCR assay, followed by a nested RT-PCR assay for sequencing and phylogenetic analysis. RESULTS: Of the 352 icterus patients included, anti-HEV IgM was found in 142 people (40.3%) and anti-HEV IgG in 175 (49.7%). Although HEV infection was detected in all age groups, there was a significant difference between the 0-10 age groups and others age groups (P = 0.001). Elevated levels of serum aminotransferase were observed in anti-HEV IgM-positive subjects. Phylogenetic analysis showed HEV genotype 1e in infected patients as well as in the contaminated water. CONCLUSION: This epidemic showed that CAR remains an HEV-endemic area. The genotype 1e strain was responsible for the HEV outbreak in Bocaranga-Koui HD. It is necessary to implement basic conditions of hygiene and sanitation to prevent further outbreaks of a HEV epidemics, to facilitate access to clean drinking water for the population, to launch intensive health education for basic hygiene measures, to sett up targeted hygiene promotion activities and, finally, to ensure that formal health care is available.

Enrichment of Geogenic Organoiodine Compounds in Alluvial-Lacustrine Aquifers: Molecular Constraints by Organic Matter.

Organoiodine compounds (OICs) are the dominant iodine species in groundwater systems. However, molecular mechanisms underlying the geochemical formation of geogenic OICs-contaminated groundwater remain unclear. Based upon multitarget field monitoring in combination with ultrahigh-resolution molecular characterization of organic components for alluvial-lacustrine aquifers, we identified a total of 939 OICs in groundwater under reducing and circumneutral pH conditions. In comparison to those in water-soluble organic matter (WSOM) in sediments, the OICs in dissolved organic matter (DOM) in groundwater typically contain fewer polycyclic aromatics and polyphenol compounds but more highly unsaturated compounds. Consequently, there were two major sources of geogenic OICs in groundwater: the migration of the OICs from aquifer sediments and abiotic reduction of iodate coupled with DOM iodination under reducing conditions. DOM iodination occurs primarily through the incorporation of reactive iodine that is generated by iodate reduction into highly unsaturated compounds, preferably containing hydrophilic functional groups as binding sites. It leads to elevation of the concentration of the OICs up to 183 µg/L in groundwater. This research provides new insights into the constraints of DOM molecular composition on the mobilization and enrichment of OICs in alluvial-lacustrine aquifers and thus improves our understanding of the genesis of geogenic iodine-contaminated groundwater systems.

Detection and molecular characterization of chicken parvovirus and chicken megrivirus in layer breeders affected by intestinal dilatation syndrome.

RESEARCH HIGHLIGHTS: IDS presented pathognomonic dilatation of the jejunum up to Meckel's diverticulum.IDS caused weight loss, decreased egg production, and increased culling and mortality.Chicken parvovirus (ChPV) was consistently detected through PCR assays.Chicken megrivirus (ChMV) was consistently detected through viral metagenomics.

Morphological and molecular characterization of Stomachicola muraenesocis Yamaguti, 1934 (Digenea: Hemiuridae) from the daggertooth pike conger Muraenesox cinereus (Forsskål).

Hemiurid digeneans conspecific with Stomachicola muraenesocis Yamaguti, 1934 (the type species of the genus Stomachicola Yamaguti, 1934) were collected from the stomach of the daggertooth pike conger Muraenesox cinereus (Forsskål) off the Persian Gulf of Iran. This study aimed to provide a detailed characterization of Stom. muraenesocis, including measurements, illustrations and scanning electron microscopy (s.e.m.) representations. Comparisons with the original and previous descriptions revealed morphological and metrical variations in several features (i.e. body size and shape, arrangement of reproductive organs, soma to ecsoma length ratio, position of genital opening, number of vitelline tubules and extension of uterine coils) between Stom. muraenesocis from different hosts and localities. This study presents the first molecular sequence data associated with the small (18S) and large (28S) subunit nuclear ribosomal RNA genes (rDNA) for Stom. muraenesocis. Phylogenetic analyses of the 18S dataset placed Stom. muraenesocis as sister lineage to a clade formed of a group of species of Lecithaster Lühe, 1901 (Lecithasteridae Odhner, 1905). In contrast, phylogenetic analyses based on the 28S consistently recovered a sister relationship between Stom. muraenesocis and representatives of the Hemiuridae Looss, 1899. Further comprehensive phylogenetically based classification in light of morphology and taxonomic history of the Hemiuridae and Lecithasteridae is required to infer phylogenetic affinities and historical biogeography of Stomachicola. A comprehensive list of previously reported species of Stomachicola together with their associated hosts, localities and morphometric data is provided.

A polyphasic molecular approach to characterize a collection of grapevine endophytic bacteria with bioprotective potential.

AIMS: The work presented here was conducted to characterize the biodiversity of a collection of bacterial isolates, mainly wood endophytes, as part of a research project focused on exploring their bioprotective potential for postharvest biological control of fruits. METHODS AND RESULTS: This work was the basis for the development of a tailored method combining 16S rDNA sequencing and Rep-PCR to differentiate the isolates and identify them to genus level or below. More than one hundred isolates obtained from wood and roots of different grapevine genotypes were cultured on appropriate growth media and then subjected to the specified multistep molecular identification. CONCLUSIONS: We have obtained good dereplication for grapevine-endophytic bacteria, together with reliable genetic identification. Both are essential prerequisites to properly characterize a biome bank and, at the same time, beneficial prerequisites to subsequently perform a correct bioprotection assessment.

Size-Resolved Molecular Characterization of Water-Soluble Organic Matter in Atmospheric Particulate Matter from Northern China.

Atmospheric particulate matter (PM) affects visibility, climate, biogeochemical cycles and human health. Water-soluble organic matter (WSOM) is an important component of PM. In this study, PM samples with size-resolved measurements at aerodynamic cut-point diameters (Dp) of 0.01-18µm were collected in the rural area of Baoding and the urban area of Dalian, Northern China. Non-targeted analysis was adopted for the characterization of the molecule constitutes of WSOM in different sized particles using Fourier transform-ion cyclotron resonance mass spectrometry. Regardless of the location, the composition of WSOM in Aitken mode particles (aerodynamic diameter < 0.05 µm) was similar. The WSOM in accumulation mode particles (0.05-2 µm) in Baoding was predominantly composed of CHO compounds (84.9%), which were mainly recognized as lignins and lipids species. However, S-containing compounds (64.2%), especially protein and carbohydrates species, accounted for most of the WSOM in the accumulation mode particles in Dalian. The CHO compounds (67.6%-79.7%) contributed the most to the WSOM in coarse mode particles (> 2 µm) from both sites. Potential sources analysis indicated the WSOM in Baoding were mainly derived from biomass burning and oxidation reactions, while the WSOM in Dalian arose from coal combustion, oxidation reactions, and regional transport.

Prevalence and molecular characterization of extended-spectrum ß-lactamase-producing Escherichia coli isolates from dairy cattle with endometritis in Gansu Province, China.

BACKGROUND: The present study aimed to investigate the prevalence and molecular characterization of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) isolated from dairy cattle with endometritis in China. The prevalence of ESBL-producing E. coli in sample was detected using ChromID ESBL agar, and genotyping of the ESBL producers was performed by PCR and DNA sequencing. RESULTS: The results revealed that the proportion of positive pathogens tested was 69.76% (180/258) in samples obtained from cows diagnosed with clinical endometritis, with E. coli accounting for 170 out of the 180 positive samples. The infection rate of isolated E. coli was 39.14% (101/258), and co-infections with other pathogens were prevalent. Furthermore, among the 158 E. coli isolates, 50 strains were identified as ESBL producers, with TEM and CTX-M prevalence rates at 78.00% and 32.00%, respectively. Drug sensitivity experiments indicated that 50 isolates of ESBL- producing E. coli were multidrug resistance (MDR), with 48.0% of them exhibiting positive results for both the class 1 integron gene and five gene cassettes associated with resistance to trimethoprim (dfr1 and dfrA17) and aminoglycosides (aadA1, aadA5, and dfrA1), respectively. CONCLUSION: This investigation demonstrated a substantial prevalence and heightened level of antimicrobial resistance among ESBL-producing E. coli isolates derived from dairy cattle infected with endometritis in China.

Advances in pediatric gliomas: from molecular characterization to personalized treatments.

Pediatric gliomas, consisting of both pediatric low-grade (pLGG) and high-grade gliomas (pHGG), are the most frequently occurring brain tumors in children. Over the last decade, several milestone advancements in treatments have been achieved as a result of stronger understanding of the molecular biology behind these tumors. This review provides an overview of pLGG and pHGG highlighting their clinical presentation, molecular characteristics, and latest advancements in therapeutic treatments.  Conclusion: The increasing understanding of the molecular biology characterizing pediatric low and high grade gliomas has revolutionized treatment options for these patients, especially in pLGG. The implementation of next generation sequencing techniques for these tumors is crucial in obtaining less toxic and more efficacious treatments. What is Known: • Pediatric Gliomas are the most common brain tumour in children. They are responsible for significant morbidity and mortality in this population. What is New: • Over the last two decades, there has been a significant increase in our global understanding of the molecular background of pediatric low and high grade gliomas. • The implementation of next generation sequencing techniques for these tumors is crucial in obtaining less toxic and more efficacious treatments, with the ultimate goal of improving both the survival and the quality of life of these patients.

Molecular Characterization of α- and ß-Thalassemia Among Children Less Than 18 Years Old in Guizhou, China.

BACKGROUND: Thalassemia is an inherited hemolytic disease, the complications and sequelae of which have posed a huge impact on both patients and society. But limited studies have investigated the molecular characterization of α- and ß-thalassemia in children from Guizhou, China. METHODS: Between January 2019 and December 2022, a total of 3301 children, aged 6 months to 18 years, suspected of having thalassemia underwent molecular analysis. RESULTS: Out of the total sample, 824 (25%) children were found to carry thalassemia mutations. The carrier rates of α-thalassemia, ß-thalassemia, and α + ß-thalassemia were determined as 8.1%, 15.6%, and 1.3%, respectively. Approximately 96.5% of the α-thalassemia gene mutations were --SEA (51%), ααCS (20.9%), -α3.7 (19.6%), and -α4.2 (5.0%). The most prevalent mutations of ß-thalassemia were ßCD17(A>T) (41.5%), ßCD41-42(-TTCT) (37.7%), and ßIVS-II-654(C>T) (11.3%). Additionally, we identified rare cases, including one case with ααHb Nunobiki/αα, two cases with triplicated α-thalassemia (one case with ααα/ααα and ßCD41-42/ßN and the other with ααα-3.7/αα and ßE CD26/ßN), and also one case with α Q-Thailandα/-α4.2 and ßCD41-42/ßN. CONCLUSIONS: Our study findings provide important insights into the heterogeneity of thalassemia carrier rates and molecular profiles among children in the Guizhou region. The findings support the development of prevention strategies to reduce the incidence of severe thalassemia in the future.

Genetics of Retinitis Pigmentosa and Other Hereditary Retinal Disorders in Western Switzerland.

INTRODUCTION: Mutational screening of inherited retinal disorders is prerequisite for gene targeted therapy. Our aim was to report and analyze the proportions of mutations in inherited retinal disease (IRD)-causing genes from a single center in Switzerland in order to describe the distribution of IRDs in Western Switzerland. METHODS: We conducted a retrospective study of patient records. Criteria for inclusion were residence in Western Switzerland for patients and relatives presenting a clinical diagnosis of IRDs and an established molecular diagnosis managed by the genetics service of the Jules-Gonin Eye Hospital (JGEH) of Lausanne between January 2002 and December 2022. We initially investigated the IRD phenotypes in all patients (full cohort) with a clinical diagnosis, then calculated the distribution of IRD gene mutations in the entire cohort (genetically determined cohort). We analyzed a sub-group that comprised pediatric patients (≤18 years of age). In addition, we calculated the distribution of gene mutations within the most represented IRDs. Comprehensive gene screening was performed using a combined approach of different generation of DNA microarray analysis, direct sequencing, and Sanger sequencing. RESULTS: The full cohort comprised 899 individuals from 690 families with a clinical diagnosis of IRDs. We identified 400 individuals from 285 families with an elucidated molecular diagnosis (variants in 84 genes) in the genetically determined cohort. The pediatric cohort included 89 individuals from 65 families with an elucidated molecular diagnosis. The molecular diagnosis rate for the genetically determined cohort was 58.2% (family ratio) and the 5 most frequently implicated genes per family were ABCA4 (11.6%), USH2A (7.4%), EYS (6.7%), PRPH2 (6.3%), and BEST1 (4.6%). The pediatric cohort had a family molecular diagnosis rate of 64.4% and the 5 most common mutated genes per family were RS1 (9.2%), ABCA4 (7.7%), CNGB3 (7.7%), CACNA1F (6.2%), CEP290 (4.6%). CONCLUSIONS: This study describes the genetic mutation landscape of IRDs in Western Switzerland in order to quantify their disease burden and contribute to a better orientation of the development of future gene targeted therapies.