35 research outputs found
Teachers' perceptions of one-to-one computing effect on learning environment in Qatari secondary schools
The purpose of this study is to examine the effect of one-to-one computing on the learning environment based upon teachers’ perceptions in Qatari secondary schools implementing the E-Schoolbag project (phase one and phase two). A questionnaire was employed to collect all teachers’ responses from ten secondary schools utilizing Tablet PC in the one-to-one computing initiative. The questionnaire assessed teachers’ perceptions about one-to-one computing in terms of: (a) student use, (b) perception of impact, (c) advantages of one-to-one computing, (d) support, (e) and classroom management issues. Teachers were found relatively positive toward the one-to-one computing initiative. Inferential analysis found no statistically significant difference for gender and years of experience in terms of perceived advantages and impact of one-to-one computing
Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy.
PURPOSE: Pathogenic autosomal recessive variants in CAD, encoding the multienzymatic protein initiating pyrimidine de novo biosynthesis, cause a severe inborn metabolic disorder treatable with a dietary supplement of uridine. This condition is difficult to diagnose given the large size of CAD with over 1000 missense variants and the nonspecific clinical presentation. We aimed to develop a reliable and discerning assay to assess the pathogenicity of CAD variants and to select affected individuals that might benefit from uridine therapy. METHODS: Using CRISPR/Cas9, we generated a human CAD-knockout cell line that requires uridine supplements for survival. Transient transfection of the knockout cells with recombinant CAD restores growth in absence of uridine. This system determines missense variants that inactivate CAD and do not rescue the growth phenotype. RESULTS: We identified 25 individuals with biallelic variants in CAD and a phenotype consistent with a CAD deficit. We used the CAD-knockout complementation assay to test a total of 34 variants, identifying 16 as deleterious for CAD activity. Combination of these pathogenic variants confirmed 11 subjects with a CAD deficit, for whom we describe the clinical phenotype. CONCLUSIONS: We designed a cell-based assay to test the pathogenicity of CAD variants, identifying 11 CAD-deficient individuals who could benefit from uridine therapy
Biallelic GRM7 variants cause epilepsy, microcephaly, and cerebral atrophy
Objective: Defects in ion channels and neurotransmitter receptors are implicated in developmental and epileptic encephalopathy (DEE). Metabotropic glutamate receptor 7 (mGluR7), encoded by GRM7, is a presynaptic G-protein-coupled glutamate receptor critical for synaptic transmission. We previously proposed GRM7 as a candidate disease gene in two families with neurodevelopmental disorders (NDDs). One additional family has been published since. Here, we describe three additional families with GRM7 biallelic variants and deeply characterize the associated clinical neurological and electrophysiological phenotype and molecular data in 11 affected individuals from six unrelated families. Methods: Exome sequencing and family-based rare variant analyses on a cohort of 220 consanguineous families with NDDs revealed three families with GRM7 biallelic variants; three additional families were identified through literature search and collaboration with a clinical molecular laboratory. Results: We compared the observed clinical features and variants of 11 affected individuals from the six unrelated families. Identified novel deleterious variants included two homozygous missense variants (c.2671G>A:p.Glu891Lys and c.1973G>A:p.Arg685Gln) and one homozygous stop-gain variant (c.1975C>T:p.Arg659Ter). Developmental delay, neonatal- or infantile-onset epilepsy, and microcephaly were universal. Three individuals had hypothalamic–pituitary–axis dysfunction without pituitary structural abnormality. Neuroimaging showed cerebral atrophy and hypomyelination in a majority of cases. Two siblings demonstrated progressive loss of myelination by 2 years in both and an acquired microcephaly pattern in one. Five individuals died in early or late childhood. Conclusion: Detailed clinical characterization of 11 individuals from six unrelated families demonstrates that rare biallelic GRM7 pathogenic variants can cause DEEs, microcephaly, hypomyelination, and cerebral atrophy. © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association
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SLC35A2â CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals
Pathogenic de novo variants in the Xâ linked gene SLC35A2 encoding the major Golgiâ localized UDPâ galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2â congenital disorders of glycosylation (CDG; formerly CDGâ IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin Nâ glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2â CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2â dependent UDPâ galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wildâ type to mutant alleles in fibroblasts from affected individuals.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/1/humu23731_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/2/humu23731-sup-0001-Supp_Mat__2019.2.10_.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150498/3/humu23731.pd
Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndromic Intellectual Disability and Deficient Histone Acetylation
Genetics of disease, diagnosis and treatmen
A decision support tool based on QFD and FMEA for the selection of manufacturing automation technologies
With the advent of the new challenge to design a more lean and responsive computer-integrated manufacturing system, firms have been striving to achieve a coherent interaction between technology, organisation, and people to meet this challenge. This paper describes an integrated approach developed for supporting management in addressing technology, organisation, and people at the earliest stages of manufacturing automation decision-making. The approach uses both the quality function deployment (QFD) technique and the failure mode and effects analysis (FMEA) technique. The principal concepts of both applications are merged together to form a decision tool; QFD in its ability to identify the most suitable manufacturing automation alternative and FMEA in its ability to identify the associated risk with that option to be addressed in the manufacturing system design and implementation phases. In addition, this paper presents the results of a practical evaluation conducted in industry
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A child with dilated cardiomyopathy and homozygous splice site variant in FLNC gene
gene encodes for Filamin-C (FLNC) protein, a sacromeric protein with important structural and signaling functions in the myocyte. Pathogenic dominant variants in
were initially linked to myofibrillar myopathy and over time, evidence showed association of this gene with different forms of autosomal dominant cardiomyopathy including hypertrophic, dilated and restrictive forms. Recently, two cases of recessive
mutations have been reported by Reinstein et al. and Kölbel et al., one with only cardiomyopathy and other with only myopathy. In this report, we describe a third case, a boy who was diagnosed at 10 years of age with shortness of breath and dilated cardiomyopathy who on sequencing was found to have a novel homozygous splice site variant (NM_001458.4 c.2122-1G>C) in
. This case suggests that the phenotype associated with variants in FLNC is very heterogenous and can be inherited in dominant or recessive forms, with later being more severe and of earlier onset
A child with dilated cardiomyopathy and homozygous splice site variant in FLNC gene
FLNC gene encodes for Filamin-C (FLNC) protein, a sacromeric protein with important structural and signaling functions in the myocyte. Pathogenic dominant variants in FLNC were initially linked to myofibrillar myopathy and over time, evidence showed association of this gene with different forms of autosomal dominant cardiomyopathy including hypertrophic, dilated and restrictive forms.Recently, two cases of recessive FLNC mutations have been reported by Reinstein et al. and Kölbel et al., one with only cardiomyopathy and other with only myopathy.In this report, we describe a third case, a boy who was diagnosed at 10 years of age with shortness of breath and dilated cardiomyopathy who on sequencing was found to have a novel homozygous splice site variant (NM_001458.4 c.2122-1G>C) in FLNC. This case suggests that the phenotype associated with variants in FLNC is very heterogenous and can be inherited in dominant or recessive forms, with later being more severe and of earlier onset
Recommended from our members
A child with dilated cardiomyopathy and homozygous splice site variant in FLNC gene
FLNC gene encodes for Filamin-C (FLNC) protein, a sacromeric protein with important structural and signaling functions in the myocyte. Pathogenic dominant variants in FLNC were initially linked to myofibrillar myopathy and over time, evidence showed association of this gene with different forms of autosomal dominant cardiomyopathy including hypertrophic, dilated and restrictive forms.Recently, two cases of recessive FLNC mutations have been reported by Reinstein et al. and Kölbel et al., one with only cardiomyopathy and other with only myopathy.In this report, we describe a third case, a boy who was diagnosed at 10 years of age with shortness of breath and dilated cardiomyopathy who on sequencing was found to have a novel homozygous splice site variant (NM_001458.4 c.2122-1G>C) in FLNC. This case suggests that the phenotype associated with variants in FLNC is very heterogenous and can be inherited in dominant or recessive forms, with later being more severe and of earlier onset