Wiedemann-Rautenstrauch Syndrome (WRS; MIM 264090) is an extremely rare and highly heterogeneous syndrome that is inherited in a recessive fashion. The patients have hallmark features such as prenatal and postnatal growth retardation, short stature, a progeroid appearance, hypotonia, facial dysmorphology, hypomyelination leukodystrophy, and mental impairment. Biallelic disease-causing variants in the RNA polymerase III subunit A (POLR3A) have been associated with WRS. Here, we report the first identified cases of WRS syndrome with novel phenotypes in three consanguineous families (two Omani and one Saudi) characterized by biallelic variants in POLR3A. Using whole-exome sequencing, we identified one novel homozygous missense variant (NM_007055: c.2456C>T; p. Pro819Leu) in two Omani families and one novel homozygous variant (c.1895G>T; p Cys632Phe) in Saudi family that segregates with the disease in the POLR3A gene. In silico homology modeling of wild-type and mutated proteins revealed a substantial change in the structure and stability of both proteins, demonstrating a possible effect on function. By identifying the homozygous variants in the exon 14 and 18 of the POLR3A gene, our findings will contribute to a better understanding of the phenotype-genotype relationship and molecular etiology of WRS syndrome.

(1) Background: The study aimed to construct a clinically valuable closet-set WRS test with a picture identification task for young Greek-speaking children. (2) Methods: The test material was meticulously designed based on specific criteria. To determine which parts of speech are used more frequently by preschool children, a spontaneous speech sample (250 words per child) was acquired from three hundred children aged 3 to 6 years (M = 4.56, SD = 0.90). The study involved the development and application of two phonemically balanced 50-word lists suitable for young children, as well as the creation of picture representations for each response set. All testing was accomplished in an audiometric booth that exceeded the audiometric rooms\' ambient noise level standards. The speech signal was routed from a laptop computer to a GSI 61 audiometer, and all test items were delivered from the audiometer to the subject. (3) Results: The results indicated that materials for a WRS test for young children are developed with high face validity and are applicable for children as young as three years old. The test satisfies the essential components needed for a WRS test. It consists of two phonemically balanced 50-word lists with low-redundancy bisyllabic words, with each list containing 227 phonemes. (5) Conclusions: This novel closed-set WRS test presents a valuable tool for assessing speech perception skills in young Greek-speaking children. The test results have various applications, including diagnosis, research, and (re)habilitation.

Wearable robots (WRs) might interact with humans in a similar manner to teammates to accomplish specific tasks together. However, the available data on WR user experience (UX) studies are limited, especially during the prototyping phase. Therefore, this study aims to examine the overall experience of WRs during the prototyping phase based on an exploratory research model. This theoretical model considered usability, hedonic quality, and attitude toward using WRs as key factors in explaining and predicting overall experience. To test the hypotheses inherent in the research model, quantitative empirical research was conducted and the data were analyzed by partial least squares structural equation modeling (PLS-SEM). The results from the PLS-SEM analysis revealed the significance level of correlations between the latent variables in the research model. The exploratory research model was able to explain up to 53.2% of the variance in the overall experience of using WRs, indicating medium predictive power. This research develops a new quantitative empirical research model that can be used to explain and predict the overall experience of interactive products such as WRs. Meanwhile, the model is needed during WR testing in the prototype phase.

Wiedemann-Rautenstrauch Syndrome (WRS), also known as neonatal progeroid syndrome, is an extremely rare genetic syndrome characterized by a senile appearance at birth with multiple complex symptoms. We reported a case of a three-days old male neonate with features of WRS presented with fatal hyperkalemic renal failure which is a unique presentation not reported before in the cases affected with this syndrome. There is a positive family history of a previous sibling with the same features who suddenly died during the first week of life. This case report aimed to increase the awareness of WRS about the features and the importance of close follow-up of the affected cases, especially in the neonatal period among neonatal physicians.

This study investigated the research trends, key areas, and directions of water rights (WRs) using bibliometric data based on the Science Citation Index Expanded (SCI-E) and Social Sciences Citation Index (SSCI). This paper presents a comprehensive review of annual output, research fields, cooperative networks, published journals, and hot spot evolution from 1971 to 2020. The results show that the number of published papers on WRs has an exponential upward trend. This research mainly focuses on water resources, environmental sciences, environmental studies, law, agronomy, and political science. Rutgerd Boelens and Barbara Van Koppen are authors of the most widely published and influential factors in the field. Leo Heller, Priscila Neves-Silva, and Jeroen Vos have been the most recently active authors. University of New Mexico and the United States Department of Agriculture are the organizations with the most publications and total citations, respectively. The USA, China, Australia, the UK, The Netherlands, and Spain are among the most productive countries for WR research. Keyword analysis showed that the study of WRs has gone through three stages: the exploration of laws and regulations, comprehensive management, and technology development and application. Literature citation cluster analysis shows that a highly central article provides a strong link between internal research on WRs. Western USA, trading WRs, and constitutional reform were hot spots before 2010, while economic anthropology, combined effect, public attitude, and integrated assessment modeling have become popular recently. The study results can help experts understand the research progress in WRs.

Objective: Wolcott-Rallison syndrome is a rare autosomal recessive inheritance disorder caused by the defectiveness of eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3), which encodes the PKR-like endoplasmic reticulum kinase (PERK). Defect in EIF2AK3 results in a permanent diabetes in early infancy or newborn period, a tendency to develop skeletal fractures and other associated disorders such as severe liver and renal dysfunction, and central hypothyroidism. Two patients with Wolcott-Rallison syndrome-like manifestations in a Chinese family and family members were genetically analyzed to identify if any variations that occurred in EIF2AK3, which may cause Wolcott-Rallison syndrome. Methods: Whole-exome sequencing (WES) was performed to identify genetic variations, and Sanger sequencing was conducted to verify the identified variations in the family members with Wolcott-Rallison syndrome (WRS) clinical manifestations. Several bioinformatics tools were employed to predict the effect of EIF2AK3 variations on the protein function. The impact on PERK protein was analyzed by sequential analysis and evolution conservation study. Results: Two novel EIF2AK3 heterozygous single base variations (c.2818C>T and c.2980G>C) were detected in the proband. PERK has two functional domains: one is regulatory domain (aa 1-576), and the other is catalytic domain (aa 577-1,115). Both variations are missense mutations and locate in catalytic domain of PERK; c.2818C>T resulted in a residue substitution of proline for serine at amino acid site 940 (p.Pro940Ser), and variation c.2980G>C caused an amino acid change at position 994 from glutamic acid to glutamine (p.Glu994Gln). These novel missense variations may affect the physiological functions of PERK protein. Conclusions: Two novel compound heterozygous EIF2AK3 variations (c.2818C>T, p.Pro940Ser and c.2980G>C, p.Glu994Gln) were found in a Chinese family. The identification of the variations and verification of their pathogenicity extended the variation spectrum of EIF2AK3 variations causing Wolcott-Rallison syndrome and enriched valuable information for precise medical intervention for Wolcott-Rallison syndrome in China.

Tryptophanyl-tRNA synthetase (WRS) is one of the aminoacyl-tRNA synthetases (ARSs) that possesses noncanonical functions. Full-length WRS is released during bacterial infection and primes the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex to elicit innate immune responses. However, the role of WRS in viral infection remains unknown. Here, we show that full-length WRS is secreted by immune cells in the early phase of viral infection and functions as an antiviral cytokine. Treatment of cells with recombinant WRS protein promotes the production of inflammatory cytokines and type I interferons (IFNs) and curtails virus replication in THP-1 and Raw264.7 cells but not in TLR4-/- or MD2-/- bone marrow-derived macrophages (BMDMs). Intravenous and intranasal administration of recombinant WRS protein induces an innate immune response and blocks viral replication in vivo These findings suggest that secreted full-length WRS has a noncanonical role in inducing innate immune responses to viral infection as well as to bacterial infection.IMPORTANCE ARSs are essential enzymes in translation that link specific amino acids to their cognate tRNAs. In higher eukaryotes, some ARSs possess additional, noncanonical functions in the regulation of cell metabolism. Here, we report a novel noncanonical function of WRS in antiviral defense. WRS is rapidly secreted in response to viral infection and primes the innate immune response by inducing the secretion of proinflammatory cytokines and type I IFNs, resulting in the inhibition of virus replication both in vitro and in vivo Thus, we consider WRS to be a member of the antiviral innate immune response. The results of this study enhance our understanding of host defense systems and provide additional information on the noncanonical functions of ARSs.

OBJECTIVE: This study describes the clinical and genetic evaluation of permanent neonatal diabetes due to Wolcott-Rallison syndrome (WRS) in south Indian consanguineous families. We aimed to evaluate the genetic basis of the disease in eight children with WRS from five South Indian families.
METHODS: We studied eight children who presented with permanent neonatal diabetes from five South Indian families. Follow up clinical evaluation revealed features (like liver disease, skeletal dysplasia, and thyroid dysfunction) suggestive of WRS. All the coding exons along with splice sites of KCNJ11, ABCC8, INS, GCK and EIF2AK3 genes were sequenced in all the probands.
RESULTS: Two novel homozygous mutations (Trp658Ser, c.3150+1G>T) and one known homozygous mutation (Arg1065*, c.3193C>T) in EIF2AK3 gene were identified in children with WRS. Mutation Arg1065*was identified in four children.
CONCLUSIONS: Our results in these families show that the mutations in homozygous state are likely to be causative. We suggest the screening for EIF2AK3 gene mutations as WRS is now recognized as the most frequent cause of neonatal diabetes in children with consanguineous parents. As the mode of inheritance is recessive, screening for genetic mutations becomes important to aid in risk prediction and clinical management.