67 research outputs found
Severe hepatopathy and neurological deterioration after start of valproate treatment in a 6-year-old child with mitochondrial tryptophanyl-tRNA synthetase deficiency
Background: The first subjects with deficiency of mitochondrial tryptophanyl-tRNA synthetase (WARS2) were reported in 2017. Their clinical characteristics can be subdivided into three phenotypes (neonatal phenotype, severe infantile onset phenotype, Parkinson-like phenotype).
Results: Here, we report on a subject who presented with early developmental delay, motor weakness and intellectual disability and who was considered during several years as having a non-progressive encephalopathy. At the age of six years, she had an epileptic seizure which was treated with sodium valproate. In the months after treatment was started, she developed acute liver failure and severe progressive encephalopathy. Although valproate was discontinued, she died six months later. Spectrophotometric analysis of the oxidative phosphorylation complexes in liver revealed a deficient activity of complex III and low normal activities of the complexes I and IV. Activity staining in the BN-PAGE gel confirmed the low activities of complex I, III and IV and, in addition, showed the presence of a subcomplex of complex V. Histochemically, a mosaic pattern was seen in hepatocytes after cytochrome c oxidase staining. Using Whole Exome Sequencing two known pathogenic variants were detected in WARS2 (c. 797delC, p. Pro266ArgfsTer10/c. 938 A > T, p. Lys313Met).
Conclusion: This is the first report of severe hepatopathy in a subject with WARS2 deficiency. The hepatopathy occurred soon after start of sodium valproate treatment. In the literature, valproate-induced hepatotoxicity was reported in the subjects with pathogenic mutations in POLG and TWNK. This case report illustrates that the course of the disease in the subjects with a mitochondrial defect can be non-progressive during several years. The subject reported here was first diagnosed as having cerebral palsy. Only after a mitochondriotoxic medication was started, the disease became progressive, and the diagnosis of a mitochondrial defect was made
Functional characterization of novel MFSD8 pathogenic variants anticipates neurological involvement in juvenile isolated maculopathy
Biallelic MFSD8 variants are an established cause of severe late-infantile subtype of neuronal ceroid lipofuscinosis (v-LINCL), a severe lysosomal storage disorder, but have also been associated with nonsyndromic adult-onset maculopathy. Here, we functionally characterized two novel MFSD8 variants found in a child with juvenile isolated maculopathy, in order to establish a refined prognosis. ABCA4 locus resequencing was followed by the analysis of other inherited retinal disease genes by whole exome sequencing (WES). Minigene assays and cDNA sequencing were used to assess the effect of a novel MFSD8 splice variant. MFSD8 expression was quantified with qPCR and overexpression studies were analyzed by immunoblotting. Transmission electron microscopy (TEM) was performed on a skin biopsy and ophthalmological and neurological re-examinations were conducted. WES revealed two novel MFSD8 variants: c.[590del];[439+3A>C] p.[Gly197Valfs*2];[Ile67Glufs*3]. Characterization of the c.439+3A>C variant via splice assays showed exon-skipping (p.Ile67Glufs*3), while overexpression studies of the corresponding protein indicated expression of a truncated polypeptide. In addition, a significantly reduced MFSD8 RNA expression was noted in patient's lymphocytes. TEM of a skin biopsy revealed typical v-LINCL lipopigment inclusions while neurological imaging of the proband displayed subtle cerebellar atrophy. Functional characterization demonstrated the pathogenicity of two novel MFSD8 variants, found in a child with an initial diagnosis of juvenile isolated maculopathy but likely evolving to v-LINCL with a protracted disease course. Our study allowed a refined neurological prognosis in the proband and expands the natural history of MFSD8-associated disease
A decade of norovirus genetic diversity in Belgium
Outbreaks of norovirus-associated gastroenteritis occur during all seasons and in various locations, and are recognized as one of the most common causes of nonbacterial food-borne infections. The molecular epidemiology of norovirus infections has not been well characterized in Belgium. To study the incidence of norovirus infections and the nature of the circulating genotypes, 3080 specimens were collected from patients with acute gastroenteritis between 2004 and 2014. Norovirus was detected with RT-PCR in 554 samples (18%). The circulating strains were genotyped based on the variability in the 5' end of the capsid gene (region C). The GII.4 genotype, which is detected predominantly worldwide, was also the most prevalent genotype in our study (87%). This study shows a high frequency and genetic diversity of norovirus in patients with acute gastroenteritis in health care facilities in Flanders, Belgium.publisher: Elsevier
articletitle: A decade of norovirus genetic diversity in Belgium
journaltitle: Infection, Genetics and Evolution
articlelink: http://dx.doi.org/10.1016/j.meegid.2014.12.001
content_type: article
copyright: Copyright © 2015 Elsevier B.V. All rights reserved.status: publishe
An experimental study on periodontal regeneration after subcutaneous transplantation of rat molar with and without cryopreservation: an in vivo study
Emergence of human G2P[4] rotaviruses containing animal derived gene segments in the post-vaccine era
The introduction of Rotarix into the Belgian immunization program in June 2006 coincided with an increase of the relative prevalence of G2P[4] strains. However, the genetic composition of these persistent G2P[4] strains has not been investigated. Therefore, we have investigated the NSP4 gene of 89 Belgian G2P[4] strains detected between 1999 and 2013, covering both pre- and post-vaccination periods. The NSP4 genes were divided over seven separate clusters of which six were more closely related to animal than to human strains. The NSP4 genes that clustered more closely to animal DS-1-like strains were isolated after 2004-2005 and were found throughout multiple seasons. Complete genome sequencing of 28 strains identified several other gene segments that clustered more closely to animal than to human DS-1-like strains. These findings suggest that frequent interspecies reassortments may have played a role in the spread of G2P[4] rotaviruses in the post-vaccination period in Belgium.status: publishe
How Cooking Time Affects In Vitro Starch and Protein Digestibility of Whole Cooked Lentil Seeds versus Isolated Cotyledon Cells
Lentils are sustainable sources of bioencapsulated macronutrients, meaning physical barriers hinder the permeation of digestive enzymes into cotyledon cells, slowing down macronutrient digestion. While lentils are typically consumed as cooked seeds, insights into the effect of cooking time on microstructural and related digestive properties are lacking. Therefore, the effect of cooking time (15, 30, or 60 min) on in vitro amylolysis and proteolysis kinetics of lentil seeds (CL) and an important microstructural fraction, i.e., cotyledon cells isolated thereof (ICC), were studied. For ICC, cooking time had no significant effect on amylolysis kinetics, while small but significant differences in proteolysis were observed (p < 0.05). In contrast, cooking time importantly affected the microstructure obtained upon the mechanical disintegration of whole lentils, resulting in significantly different digestion kinetics. Upon long cooking times (60 min), digestion kinetics approached those of ICC since mechanical disintegration yielded a high fraction of individual cotyledon cells (67 g/100 g dry matter). However, cooked lentils with a short cooking time (15 min) showed significantly slower amylolysis with a lower final extent (~30%), due to the presence of more cell clusters upon disintegration. In conclusion, cooking time can be used to obtain distinct microstructures and digestive functionalities with perspectives for household and industrial preparation
Emergence of human G2P[4] rotaviruses containing animal derived gene segments in the post-vaccine era
The introduction of Rotarix into the Belgian immunization program in June 2006 coincided with an increase of the relative prevalence of G2P[4] strains. However, the genetic composition of these persistent G2P[4] strains has not been investigated. Therefore, we have investigated the NSP4 gene of 89 Belgian G2P[4] strains detected between 1999 and 2013, covering both pre- and post-vaccination periods. The NSP4 genes were divided over seven separate clusters of which six were more closely related to animal than to human strains. The NSP4 genes that clustered more closely to animal DS-1-like strains were isolated after 2004-2005 and were found throughout multiple seasons. Complete genome sequencing of 28 strains identified several other gene segments that clustered more closely to animal than to human DS-1-like strains. These findings suggest that frequent interspecies reassortments may have played a role in the spread of G2P[4] rotaviruses in the post-vaccination period in Belgium.status: publishe
Erratum: Emergence of human G2P[4] rotaviruses containing animal derived gene segments in the post-vaccine era
status: publishe
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