Search Results (3,874)

Hereditary ataxias are a highly heterogenous group of diseases characterized by loss of coordination. In this study, we investigated a family of random-bred dogs, in which two siblings were affected by a slowly progressive ataxia. They presented with clinical signs of progressive cerebellar ataxia, hypermetria, and absent menace response. The MRI revealed generalized brain atrophy, reduced cortical demarcation, hypoplastic corpus callosum, and cerebellar folia thinning, highly suggestive of a neurodegenerative disorder. We sequenced the genomes of the two affected dogs and their unaffected parents. Filtering for protein-changing variants that had homozygous alternate genotypes in the affected dogs, heterozygous genotypes in the parents, and homozygous reference genotypes in 1576 control genomes yielded a single missense variant in the RAB24 gene, XM_038534663.1:c.239G>T or XP_038390591.1:p.(Gly80Val). Genotypes at this variant showed the expected co-segregation with the ataxia phenotype in the investigated family. The predicted amino acid affects the conserved RabF4 motif. Glycine-80 resides at the protein surface and the introduction of a hydrophobic isopropyl side chain of the mutant valine might impede solvent accessibility. Another missense variant in RAB24, p.Glu38Pro, was previously reported to cause a clinically similar form of cerebellar ataxia in Gordon Setters and Old English Sheepdogs. Taken together, the available data suggest that RAB24:p.Gly80Val represents the causal variant in the studied dogs. To the best of our knowledge, this is only the second report of a potentially pathogenic RAB24 variant in any species and further supports that RAB24 should be considered a candidate gene in human ataxia patients with unclear molecular etiology. Full article

Background/Objectives: Children with severe physical and communication disabilities face many challenges. They have very limited opportunities for upright, hands-free, self-initiated mobility. Current findings in neuroscience and theories on child development suggest that self-initiated mobility can have positive cascading effects on various developmental areas, including language and communication. This study was conducted to examine the current use of hands-free support walkers with children who have severe physical and communication disabilities and use augmentative and alternative communication and to identify the benefits and problems perceived by their parents and professionals from different disciplines. Methods: Online surveys were utilized to collect information from 127 participants, including 31 parents and 96 professionals or paraprofessionals. Results: The participants reported that these children could perform various motor activities in the hands-free support walkers to achieve different goals. Benefits identified by both parents and professionals included providing a way to exercise and stay active, improving motor control, enhancing independence, and bringing enjoyment. Professionals also observed positive impacts on communication, vocalization, use of eye contact, and problem solving. Conclusions: Results suggest that children with severe physical and communication disabilities can benefit from the upright, hands-free, self-initiated mobility provided by hands-free support walkers. Clinical implications and needs for future research are discussed. Full article

Research highlights a growing demand for active, experiential learning methods in higher education, especially in teacher education. While the benefits of parental involvement (PI) are well-documented, Hungary lacks tools to effectively prepare teacher trainees for fostering family–school cooperation. This study addresses this gap by introducing a custom-designed board game as an innovative teaching tool. The game simulates real-world challenges in PI through a cooperative, scenario-based framework. Exercises are grounded in international and national research, ensuring their relevance and evidence-based design. Tested with 110 students, the game’s educational value was assessed via post-gameplay questionnaires. Participants emphasized the strengths of its cooperative structure, realistic scenarios, and integration of humor. Many reported gaining new insights into parental roles and strategies for effective home–school partnerships. Practical applications include integrating the game into teacher education curricula and adapting it for other educational contexts. This study demonstrates how board games can bridge theory and practice, offering an engaging, effective medium to prepare future teachers for the challenges of PI. Full article

Background: Self-report physical activity (PA) scales, accelerometry, and heart rate (HR) monitoring are reliable tools for PA measurement for children with cerebral palsy (CP); however, there are limitations for those who are primary wheelchair users. The purpose of our study was to evaluate face and construct validity of the PROMIS^® Pediatric PA parent proxy short form 8a in measuring PA amount and intensity in children with CP who are non-ambulatory. Methods: Face validity: Semi-structured interviews with parents and pediatric physical therapists (PTs) were conducted about the appropriateness of each item on the PROMIS^® Pediatric PA short form. Construct validity: Children with CP who were non-ambulatory participated in a one-week observational study. PA amount and intensity were examined using PA monitors (Actigraph GT9X) and HR monitors (Fitbit Charge 4). Activity counts and time in sedentary and non-sedentary intensity zones were derived and compared to the PROMIS^® T-scaled score. Results: Twenty-two physical therapists (PTs) and fifteen parents participated in the interviews, and ten children completed 1-week PA observation. Eight and seven participants completed sufficient time of uninterrupted PA and HR monitor wear, respectively. Parents and PTs agreed that several questions were not appropriate for children with CP who were non-ambulatory. PA intensity via activity counts derived from wrist worn monitors showed a strong positive correlation with the PROMIS^® PA measure. Conclusions: Construct validity in our small sample was established between PROMIS^® scores and accelerometry activity counts when documenting PA amount and intensity; however, there were some differences on PROMIS^® face validity per parent and PT respondents. Despite some concerns regarding face validity, the PROMIS^® Pediatric PA parent proxy short form 8a shows promise as a valid measure of physical activity amount and intensity in non-ambulatory children with CP, warranting further investigation and refinement. Full article

In December 2023, infections of western equine encephalitis virus (WEEV) within Argentina were reported to the World Health Organization (WHO). By April 2024, more than 250 human infections, 12 of which were fatal, and 2500 equine infections were identified in South America. Laboratory diagnosis and surveillance in affected countries were hindered by a lack of facilities equipped with BSL-3 laboratories, as confirmatory serodiagnosis for WEEV requires live virus in the plaque reduction neutralization test (PRNT). To expand serodiagnosis for WEEV in the Americas, we developed a virus chimera composed of vesicular stomatitis virus (VSV) engineered to display the E2-E1 glycoproteins of WEEV (VSV/WEEV) in place of the VSV glycoprotein (G). PRNT₉₀ and IC₉₀ values of parental WEEV and VSV/WEEV were analogous using sera collected from mice, horses, and chickens. VSV/WEEV rapidly formed plaques with clear borders and reduced the assay readout time by approximately 8 h compared to the parental virus. Overall, we demonstrate that chimeric VSV/WEEV is a suitable surrogate for WEEV in a diagnostic PRNT. Use of chimeric VSV/WEEV in place of authentic WEEV will dramatically expand testing capacity by enabling PRNTs to be performed at BSL-2 containment, while simultaneously decreasing the health risk to testing personnel. Full article

Parental school involvement (PSI) is an important contributor to children’s academic and overall positive development. Such activities as discussing schoolwork and tracking progress can boost children’s motivation and achievements. Although the multifaceted nature of PSI is widely recognized, there are limited reliable measures that comprehensively capture all its dimensions, particularly for children and adolescents. This study aims to develop a measure for assessing children and adolescents’ perceptions of parental involvement based on parent- and teacher-validated self-report measures—the Parental School Involvement Questionnaire—Children’s version (PSIQ-CV). A total of 537 children and adolescents (M_Age = 9.64, SD_Age = 2.43), mainly female (52.8%), from the south of Portugal participated in this study. An exploratory factor analysis (EFA, n = 150) and a confirmatory factor analysis (CFA, n = 387) were carried out. The EFA indicated a three-factor solution (i.e., support in learning activities, parent–school communication, and supervision), supported by the CFA, with good quality-of-fit indices (χ² = 225; df = 101; χ²/df = 2.23; CFI = 0.91; TLI = 0.89; RMSEA = 0.060 [CI: 0.049–0.070]). Our data confirmed that the PSIQ-CV has robust psychometric properties, with acceptable reliability and validity. The PSIQ-CV can be considered a relevant and valid tool for measuring the perception of parental school involvement among children and adolescents, in line with Epstein’s theoretical model, and useful for both researchers and practitioners. Full article

Background/Objectives: Chickenpox is an ongoing health threat for young children. This study aimed to investigate varicella vaccination uptake among children and its determinants at both the individual and interpersonal levels. Methods: A cross-sectional survey of parents of children aged 0–15 years and with administrative health records was conducted between September and October 2024 in Shenzhen, China. Participants were recruited through multistage random sampling. This analysis was based on a subsample of 996 parents whose children were 1–10 years old and without a prior history of chickenpox. Multivariate logistic regression models were fitted. Results: Among the participants, 47.0% reported that their children had received a varicella vaccination. Parents who believed that chickenpox was highly contagious (adjusted odds ratios [AOR]: 1.62, 95% confidence interval [CI]: 1.23, 2.13), perceived more benefits (AOR: 1.22, 95% CI: 1.05, 1.41) and cues to action (AOR: 1.33, 95% CI: 1.04, 1.69), and exhibited greater self-efficacy (AOR: 1.40, 95% CI: 1.09, 1.80) related to children’s varicella vaccination reported higher varicella vaccination uptake for their children. Greater perceived barriers related to vaccination (AOR: 0.89, 95% CI: 0.83, 0.95) and dysfunctional interactions with children (AOR: 0.97, 95% CI: 0.94, 0.99) were associated with lower varicella vaccination uptake for children. In addition, higher exposure to information encouraging parents to vaccinate their children against chickenpox (AOR: 1.24, 95%CI: 1.08, 1.41) and thoughtful consideration of the veracity of the information were associated with higher varicella vaccination uptake among children (AOR: 1.19, 95% CI: 1.05, 1.36). Conclusions: There is a strong need to promote varicella vaccination for children in China. Full article

Background/Objectives: While ocular albinism (OA) is usually associated with reduced vision, nystagmus, and foveal hypoplasia, there is phenotypic variability in iris and fundus hypopigmentation. Hemizygous pathogenic/likely pathogenic (P/LP) variants in GPR143 at X: 151.56–151.59 have been shown in the literature to be associated with OA. The purpose of this study was to report the case of a Hispanic male with X-linked inherited OA associated with a hemizygous GPR143 variant and to review the literature relating to genotype–phenotype associations with GPR143 and OA. Methods: After consent to an IRB-approved protocol, a 14-year-old Hispanic male patient with OA and his parents underwent whole genome sequencing (WGS) in 2023. Two maternal uncles with nystagmus underwent targeted variant testing in 2024. A literature review of reported GPR143 variants was completed. Results: A male with reduced visual acuity, infantile-onset nystagmus, foveal hypoplasia, and iris hypopigmentation was identified to have the variant GPR143, c.455+3A>G, which was also present in his mother and two affected maternal uncles. This variant has been previously identified in other Hispanic patients of Mexican descent. Additionally, 127 variants were identified in the literature and reported to be associated with OA. All patients had reduced visual acuity (average 0.71 ± 0.23 logMAR), 99% had nystagmus, 97% foveal hypoplasia, 79% fundus hypopigmentation, and 71% iris hypopigmentation. Of those patients with reported optotype best corrected visual acuity (BCVA), eight (9%) had VA from 20/25 to 20/40, 24 (24%) had VA from 20/50 to 20/80, and 63 (67%) had VA from 20/100 to 20/200. The most frequent type of variant was missense (31%, n = 39). Frameshift and nonsense variants were associated with the lowest rates of iris hypopigmentation (50% [n = 11] and 44% [n = 8], respectively; p = 0.0068). Conclusions: This case represents phenotypic variability of GPR143-associated OA and highlights the importance of repeat genetic testing and independent analyses of test results for accurate variant classification, particularly in non-White and Hispanic patients. Further studies in more diverse populations are needed to better develop genotype–phenotype associations for GPR143-associated OA. Full article

Background/Objectives: Despite the importance of parent mental health for child health, there are no global prevalence data on parental mental health symptoms when children are hospitalized. We aimed to describe depression and anxiety symptom prevalence and associated factors among parents of hospitalized children. Methods: We conducted this 14-country prospective cohort survey with parents/primary caregivers staying at a nearby Ronald McDonald House^® during their child’s hospital treatment. We used the Hospital Anxiety and Depression Scale to measure depression and anxiety symptoms and validated scales and theory-based questions to measure parent, family, and child covariates. We calculated the prevalence of clinically significant or concerning symptoms of depression and anxiety, and used multivariable regression analyses to examine associations between covariates and outcomes. Results: Among 3350 participants, 1789 (49.7%) reported depression symptoms and 2286 (69.0%) reported anxiety symptoms. Worry about housing and poorer ratings of their child’s health were associated with increased risk of depression symptoms. Poorer rating of the child’s health, living with a partner, and discrimination in daily life were associated with increased risk of anxiety symptoms. Higher levels of self-care, hospital family-centered care, and social support were associated with reduced risk of depression symptoms. Higher levels of self-care and social support were associated with reduced risk of anxiety symptoms. Conclusions: Clinically significant or concerning depression and anxiety symptoms are common among parents of hospitalized children globally. Hospitals should consider offering routine mental health symptom screening and preventative mental health and support services to all parents. Full article

Background/Objectives: Internalizing disorders are highly prevalent during adolescence. Previous research has shown that psychological inflexibility (PI) in both adolescents and their parents contributes to internalizing problems. However, how parental and adolescent PI relate to one another in explaining these difficulties remains unclear. The present exploratory study examined whether adolescent PI mediates the relationship between maternal PI and internalizing problems in adolescents. Methods: The study sample included 81 mother–adolescent dyads (80% female adolescents). Mothers completed a general self-report measure of PI, while adolescents completed self-report measures assessing both PI and internalizing problems. Results: The results showed that adolescent PI partially mediated the relationship between maternal PI and internalizing difficulties in female adolescents, whereas the mediation model was not significant for male adolescents. Conclusions: Findings suggest that mothers with high levels of psychological inflexibility may foster similar patterns in their children, particularly in daughters, thereby increasing adolescents’ vulnerability to increased psychological distress. Full article

Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article

Conventional methods for generating knock-out or knock-in mammalian cell models using CRISPR-Cas9 genome editing often require tedious single-cell clone selection and expansion. In this study, we develop and optimise rapid and robust strategies to engineer homozygous fluorescent reporter knock-in cell pools with precise genome editing, circumventing clonal variability inherent to traditional approaches. To reduce false-positive cells associated with random integration, we optimise the design of donor DNA by removing the start codon of the fluorescent reporter and incorporating a self-cleaving T2A peptide system. Using fluorescence-assisted cell sorting (FACS), we efficiently identify and isolate the desired homozygous fluorescent knock-in clones, establishing stable cell pools that preserve parental cell line heterogeneity and faithfully reflect endogenous transcriptional regulation of the target gene. We evaluate the knock-in efficiency and rate of undesired random integration in the electroporation method with either a dual-plasmid system (sgRNA and donor DNA in two separate vectors) or a single-plasmid system (sgRNA and donor DNA combined in one vector). We further demonstrate that coupling our single-plasmid construct with an integrase-deficient lentivirus vector (IDLV) packaging system efficiently generates fluorescent knock-in reporter cell pools, offering flexibility between electroporation and lentivirus transduction methods. Notably, compared to the electroporation methods, the IDLV system significantly minimises random integration. Moreover, the resulting reporter cell lines are compatible with most of the available genome-wide sgRNA libraries, enabling unbiased CRISPR screens to identify key transcriptional regulators of a gene of interest. Overall, our methodologies provide a powerful genetic tool for rapid and robust generation of fluorescent reporter knock-in cell pools with precise genome editing by CRISPR-Cas9 for various research purposes. Full article

In China, grandparents play a significant role in childrearing. This study aims to identify latent profiles of intergenerational parenting styles and explore their impact on grandchildren’s behavioral outcomes. A total of 1432 Chinese children (M_age = 12.58 years; 45.25% boys) completed questionnaires assessing perceived grandparenting styles, while fathers and mothers independently reported their own parenting practices. Latent Profile Analysis (LPA) identified three distinct parenting profiles: “Grandparents Positive–Parents Negative” (GP–PN, 18.37%), “Grandparents Positive–Parents Positive” (GP–PP, 59.15%), and “Grandparents Negative–Parents Positive” (GN–PP, 22.48%). Regression analyses revealed that the number of siblings, grade level, and grandparent type could significantly predict profile membership. Notably, consistent and positive intergenerational parenting styles were associated with fewer problem behaviors in children. Furthermore, the relationship between parenting profiles and problem behaviors was mediated by the quality of the grandparent–parent relationship. These findings suggested that grandparents and parents should coordinate their parenting styles when raising grandchildren together. Full article

Background/Objectives: Pseudohypoparathyroidism (PHP) is a group of genetic disorders characterized by end-organ resistance to multiple hormones, short stature, brachydactyly, subcutaneous ossifications, obesity, and developmental delays. The tissue specific imprinting of GNAS in the hypothalamus may lead to different eating behavior phenotypes in maternally inherited (PHP1A, PHP1B) vs. paternally inherited (PPHP) variants. In this exploratory study, we aimed to evaluate differences in eating behaviors in a cohort of patients with PHP1A, PPHP and PHP1B. Methods: Assessments included caregiver-reported measures (hyperphagia questionnaire, children’s eating behavior questionnaire, child feeding questionnaire) and self-reported measures (three factor eating behavior questionnaire). Results: A total of 58 patients with PHP1A, 13 patients with PPHP and 10 patients with PHP1B contributed data, along with 124 obese pediatric controls. An increased risk of obesity was found in PHP1A vs. PPHP (adult body mass index (BMI) 39.8 ± 8.7 vs. 30.2 ± 7.4 kg/m², p = 0.03). Parents reported significantly earlier onset of interest in food in children with PHP1A (2.0 ± 2.3 years) and PHP1B (1.1 ± 1.3 years) compared with controls (5.2 ± 3.2 years, p < 0.001). Measures of hyperphagia, satiety and other feeding behaviors were all similar to controls. The highest hyperphagia questionnaire scores were seen prior to adolescence. In a multi-year, longitudinal assessment of 11 pediatric patients with PHP1A, hyperphagia scores were stable and 25% showed an improvement in symptoms. Conclusion: Patients with PHP1A/1B may have hyperphagia symptoms from a young age but they do not worsen over time. Patients may overeat when allowed access to food, but do not usually have disruptive food seeking behaviors. Early diagnosis can give clinicians the opportunity to provide anticipatory diagnosis on the increased risk of obesity in PHP1A/1B and need for scheduled meals and controlled portions. Further studies with larger cohorts are needed to confirm these findings. Full article

Background/Objectives: The objective of this study was to validate a new parent-reported scale for tracking Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is a condition characterized by a sudden and severe onset of neuropsychiatric symptoms. To meet diagnostic criteria, an individual must present with either obsessive–compulsive disorder (OCD) or severely restricted food intake, accompanied by at least two additional cognitive, behavioral, or emotional symptoms. These may include anxiety, emotional instability, depression, irritability, aggression, oppositional behaviors, developmental or behavioral regression, a decline in academic skills such as handwriting or math, sensory abnormalities, frequent urination, and enuresis. The onset of symptoms is usually triggered by an infection or an abnormal immune/inflammatory response. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a subtype of PANS specifically linked to strep infections. Methods: We developed a 101-item PANS/PANDAS and Related Inflammatory Brain Disorders Treatment Evaluation Checklist (PTEC) designed to assess changes to a patient’s symptoms over time along 10 subscales: Behavior/Mood, OCD, Anxiety, Food intake, Tics, Cognitive/Developmental, Sensory, Other, Sleep, and Health. The psychometric quality of PTEC was tested with 225 participants. Results: The internal reliability of the PTEC was excellent (Cronbach’s alpha = 0.96). PTEC exhibited adequate test–retest reliability (r = 0.6) and excellent construct validity, supported by a strong correlation with the Health subscale of the Autism Treatment Evaluation Checklist (r = 0.8). Conclusions: We hope that PTEC will assist parents and clinicians in the monitoring and treatment of PANS. The PTEC questionnaire is freely available at neuroimmune.org/PTEC. Full article