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1.
Brain Res ; 1834: 148912, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38575106

ABSTRACT

Multiple system atrophy (MSA) is a rare, neurodegenerative disorder with rapid motor and non-motor symptom progression. MSA is characterized by protein aggregations of α-synuclein found in the cytoplasm of oligodendrocytes. Despite this pathological hallmark, there is still little known about the cause of this disease, resulting in poor treatment options and quality of life post-diagnosis. In this study, we investigated differentially expressed genes (DEGs) via RNA-sequencing of brain samples from a validated PLP-α-synuclein transgenic mouse model, identifying a total of 40 DEGs in the PLP group compared to wild-type (WT), with top detected genes being Gm15446, Mcm6, Aldh7a1 and Gm3435. We observed a significant enrichment of immune pathways and endothelial cell genes among the upregulated genes, whereas downregulated genes were significantly enriched for oligodendrocyte and neuronal genes. We then calculated possible overlap of these DEGs with previously profiled human MSA RNA, resulting in the identification of significant downregulation of the Tsr2 gene. Identifying key gene expression profiles specific to MSA patients is crucial to further understanding the cause, and possible prevention, of this rapidly progressive neurodegenerative disorder.


Subject(s)
Disease Models, Animal , Mice, Transgenic , Multiple System Atrophy , Transcriptome , alpha-Synuclein , Animals , Humans , Mice , alpha-Synuclein/genetics , alpha-Synuclein/metabolism , Brain/metabolism , Mice, Inbred C57BL , Multiple System Atrophy/genetics , Myelin Proteolipid Protein/genetics , Oligodendroglia/metabolism , Male , Female
2.
BMC Vet Res ; 17(1): 215, 2021 Jun 10.
Article in English | MEDLINE | ID: mdl-34112165

ABSTRACT

BACKGROUND: The popularity of new world camelids, particularly alpacas, is growing rapidly in Ireland, presenting a clinical challenge to veterinary practitioners who may not have worked with these species previously. To the authors' knowledge, the clinical course of a case of acute fasciolosis in an alpaca has not previously been reported, and fasciolosis has not been reported at all in alpacas in Ireland, making this case report a valuable addition to the current literature. CASE PRESENTATION: A three-year-old male castrated huacaya alpaca was admitted to UCD Veterinary Hospital with a two-day history of colic and tenesmus. He had been treated with albendazole, dexamethasone and potentiated amoxycillin by the referring veterinary practitioner with no response. On initial clinical exam, sensitivity to abdominal palpation was the only abnormality. However, the alpaca proceeded to show abnormal lying positions, tenesmus and reduced faecal output over the next 24 h. A general blood panel demonstrated moderate anaemia, marked hyperglobulinaemia and moderately increased hepatocellular and hepatobiliary enzyme activity. Abdominal radiography revealed enlargement of the first forestomach compartment without evidence of gastrointestinal obstruction or peritonitis. An abdominal ultrasound exam revealed an elongated, heterogenous mass in the caudoventral abdomen that appeared to be contiguous with the liver. FNA of this mass revealed that it was in fact a liver lobe with biliary stasis and inflammation. Faecal sedimentation demonstrated Fasciola hepatica eggs. In spite of treatment with triclabendazole and supportive treatment including blood transfusion, the alpaca's condition continued to deteriorate and he was euthanised. On post-mortem exam, acute fasciolosis was diagnosed. CONCLUSIONS: The clinical presentation and course of a case of acute fasciolosis in an individual alpaca is described, including the results of a range of diagnostic tests that were carried out. The final diagnosis is supported by a description of post-mortem findings. This information will serve as a resource for veterinary practitioners involved in the diagnosis and treatment of similar cases.


Subject(s)
Camelids, New World , Fascioliasis/veterinary , Acute Disease , Amoxicillin/therapeutic use , Animals , Anti-Bacterial Agents/therapeutic use , Antiplatyhelmintic Agents/therapeutic use , Colic/parasitology , Colic/veterinary , Fascioliasis/diagnosis , Fascioliasis/drug therapy , Ireland , Male , Treatment Outcome , Triclabendazole/therapeutic use
3.
Am J Med Genet A ; 173(3): 611-617, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28139025

ABSTRACT

Mutations in CASK cause X-linked intellectual disability, microcephaly with pontine and cerebellar hypoplasia, optic atrophy, nystagmus, feeding difficulties, GI hypomotility, and seizures. Here we present a patient with a de novo carboxyl-terminus splice site mutation in CASK (c.2521-2A>G) and clinical features of the rare FG syndrome-4 (FGS4). We provide further characterization of genotype-phenotype correlations in CASK mutations and the presentation of nystagmus and the FGS4 phenotype. There is considerable variability in clinical phenotype among patients with a CASK mutation, even among variants predicted to have similar functionality. Our patient presented with developmental delay, nystagmus, and severe gastrointestinal and gastroesophageal complications. From a cognitive and neuropsychological perspective, language skills and IQ are within normal range, although visual-motor, motor development, behavior, and working memory were impaired. The c.2521-2A>G splice mutation leads to skipping of exon 26 and a 9 base-pair deletion associated with a cryptic splice site, leading to a 28-AA and a 3-AA in-frame deletion, respectively (p.Ala841_Lys843del and p.Ala841_Glu868del). The predominant mutant transcripts contain an aberrant guanylate kinase domain and thus are predicted to degrade CASK's ability to interact with important neuronal and ocular development proteins, including FRMD7. Upregulation of CASK as well as dysregulation among a number of interactors is also evident by RNA-seq. This is the second CASK mutation known to us as cause of FGS4. © 2017 Wiley Periodicals, Inc.


Subject(s)
Agenesis of Corpus Callosum/diagnosis , Agenesis of Corpus Callosum/genetics , Anus, Imperforate/diagnosis , Anus, Imperforate/genetics , Constipation/diagnosis , Constipation/genetics , Guanylate Kinases/genetics , Mental Retardation, X-Linked/diagnosis , Mental Retardation, X-Linked/genetics , Muscle Hypotonia/congenital , Mutation , Nystagmus, Congenital/diagnosis , Nystagmus, Congenital/genetics , RNA Splice Sites , Adolescent , Child , Child, Preschool , Facies , Female , Gene Expression , Genetic Association Studies , High-Throughput Nucleotide Sequencing , Humans , In Situ Hybridization, Fluorescence , Male , Muscle Hypotonia/diagnosis , Muscle Hypotonia/genetics , Neuropsychological Tests , Phenotype , Polymorphism, Single Nucleotide
4.
Brain Behav Immun ; 38: 91-9, 2014 May.
Article in English | MEDLINE | ID: mdl-24389156

ABSTRACT

Circulating 45 and 62kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N=355), their unaffected siblings (N=142) and mothers (N=333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62kDa antibodies are correlated with autism severity: the 45kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P<0.05). On the other hand, maternal 37, 39 and 73kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P<0.05). Presence of the 62kDa autoAb in the child is significantly associated with presence of the 39 and/or 73kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for anti-brain antibodies in autism while demonstrating their familial clustering.


Subject(s)
Autoantibodies/blood , Brain/immunology , Child Development Disorders, Pervasive/immunology , Adolescent , Adult , Autoantibodies/immunology , Autoimmunity , Child , Child, Preschool , Female , Humans , Italy , Male , Middle Aged , Young Adult
5.
J Biosoc Sci ; 42(2): 201-11, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19895728

ABSTRACT

This study evaluated the prevalence of overweight and obesity in the male Sardinian population (Italy), and verifies that it has increased over the last 30 years. Data were collected during 2003-2004 from military registers in the Archive of the Military District of Cagliari for the years 1969 and 1998. A total of 22,345 forms were analysed from all Sardinia. The conscripts were classified on the basis of their place of residence and socioeconomic status. The overall prevalence of overweight and obesity in Sardinia were 4.33% and 0.55%, respectively, for the conscripts of 1969 and 9.8% and 3% for 1998. Olbia-Tempio (northern Sardinia) was the province with the highest incidence of overweight and obesity in 1969, and Nuoro (central Sardinia) had the highest incidence in 1998. Distribution of body mass index, overweight and obesity across the island showed a statistically significant heterogeneity that strongly decreased from 1969 to 1998. Among the conscripts of 1969, the incidence of overweight and obesity were higher in rural than in urban regions. An opposite trend was observed for the 1998 prevalence, it being more frequent in urban than rural regions. Comparison with other Italian regions was made. The percentages of overweight and obese individuals in Sardinia have markedly increased during the last 30 years, but their low incidence with respect to other Italian populations could be explained by the genetic peculiarity of the island. The change in the internal distribution of obesity clearly reflects socioeconomic changes.


Subject(s)
Military Personnel/statistics & numerical data , Obesity/epidemiology , Overweight , Adolescent , Body Mass Index , Catchment Area, Health , Humans , Incidence , Italy/epidemiology , Male , Prevalence
6.
Exp Mol Pathol ; 86(2): 136-7, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19103196

ABSTRACT

In this work we investigated about the presence of a correlation between a (CA)n repeat located in exon 29 of NOS1 gene and the beta-thalassemia trait in Corsica Island (France). We genotyped a sample of individuals with beta-thalassemia minor (N=110) and an ethnically matched control (N=113) from Balagna, a region of Corsica Island (France). Results highlighted the high frequencies of allele with 16 and 17 repeats in the thalassemic sample. From these results we suggest, that high frequencies of alleles with 16 and 17 repeats, could be a consequence of past malarial endemicity.


Subject(s)
Alleles , Geography , Heterozygote , Nitric Oxide Synthase Type I/genetics , Polymorphism, Genetic , Repetitive Sequences, Nucleic Acid/genetics , beta-Thalassemia/genetics , Case-Control Studies , France , Genotype , Humans , beta-Thalassemia/enzymology
7.
Exp Mol Pathol ; 83(3): 490-2, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17916351

ABSTRACT

In this study we analyzed allele and genotype distributions of 24 bp duplication of the CHIT1 gene in a sample of patients (N=300) with coronary artery disease (CAD) and in a control group (N=300) from central Corsica (France), with the aim to investigate the possible association between CHIT1 genotypes and CAD in Corsican population. Serum chitotriosidase activity is increased in individuals experiencing an ischemic stroke of atherothrombotic etiology and in subjects with ischemic heart disease. Our results suggest that 24 bp duplication of CHIT1 gene is not correlated with CAD in Corsican population, according to a previous study carried out on a Spanish sample. Gene prevalence and perhaps gene-disease associations vary according to ethnicity. Further studies, based on different ethnic groups, could be suitable to determine the implication of this polymorphism with respect to CAD.


Subject(s)
Coronary Artery Disease/genetics , Gene Duplication , Hexosaminidases/genetics , Polymorphism, Genetic , Adult , Female , France , Genetic Predisposition to Disease , Genotype , Hexosaminidases/blood , Humans , Male , Middle Aged , Statistics as Topic
9.
Exp Mol Pathol ; 83(1): 25-9, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17275808

ABSTRACT

The aim of the present study was to investigate the association between coronary artery disease (CAD) and Cholesterol Ester Transfer Protein (CETP) (gaaa)n polymorphisms of the CETP gene in Central Corsica island (France). The study group was composed by 300 unrelated Corsican patients with angiographically documented CAD and 300 unrelated healthy blood donors. Significant differences were observed in the distribution of CETP (gaaa)n alleles between the groups under study (p=0.03; chi(2): 16.8, df: 8). The occurrence of a long allele (408 bp) was higher in cases (12%) than in control group (2%), showing a 6.75-fold increased risk for CAD in Corsica patients (p=0.0055; OR=6.750; 95% CIs=1.47-31.00). The correlation of this polymorphism with the lipid profile (cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides) in the patients group was determined. There was a significant association of the long alleles of CETP (gaaa)n with HDL-C levels. In the patient and in the control groups the LL genotypes had lower HDL-C compared with the SS and SL genotypes (p<0.0001). In summary our results suggest that the genetic variation at the CETP gene may play an important role in determining CAD in Corsican population.


Subject(s)
Cholesterol Ester Transfer Proteins/genetics , Coronary Artery Disease/genetics , Polymorphism, Genetic/genetics , Alleles , Coronary Artery Disease/epidemiology , Coronary Artery Disease/pathology , Female , France/epidemiology , Humans , Lipids/blood , Male , Middle Aged
10.
Am J Hum Biol ; 17(6): 765-72, 2005.
Article in English | MEDLINE | ID: mdl-16254903

ABSTRACT

Seven polymorphic sites in the beta-globin cluster in association with specific thalassemia mutations were analyzed in a sample from Sardinia, Italy. In order to verify previous works carried out on normal samples (beta(A)/beta(A)) and family studies on beta-thalassemia homozygotes individuals, the haplotype frequencies in both normal individuals (beta(A)/beta(A)) and beta(0)39-thalassemia carriers (beta(A)/beta0) were studied. In our work chromosomes carrying beta(0)39 mutation are characterized by a prevalence of haplotype II (- + + - + + +) (52%) relative to haplotype I (+- - - - + +) (29%), in contrast, among chromosomes with beta(A) the frequency of haplotype I is much greater than that of haplotype II. These data confirm what was found by other authors. Nevertheless, our results disagree with those of previous studies of Sardinians, both in frequencies values and in the numbers of haplotypes identified. Population analysis performed with samples carrying the beta-thalassemic mutation highlighted the peculiarity of Sardinians with respect to other Mediterranean populations. The Corsican population is most similar to the Sardinian population, confirming previous analyses performed with both classical markers and mitochondrial and genomic DNA.


Subject(s)
Codon, Nonsense/genetics , DNA/genetics , Globins/genetics , beta-Thalassemia/genetics , Adult , Female , Gene Frequency , Genetic Predisposition to Disease , Globins/metabolism , Haplotypes , Humans , Italy/epidemiology , Male , Polymerase Chain Reaction , Polymorphism, Genetic , Prevalence , beta-Thalassemia/blood , beta-Thalassemia/epidemiology
11.
Exp Mol Pathol ; 79(3): 210-3, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16248996

ABSTRACT

We have investigated the frequencies of seven markers among 100 unrelated individuals with angiographically documented CAD (Coronary Artery Disease) and among 100 unrelated healthy blood donors in the central region of Corsica island (France). The seven polymorphisms analyzed were chosen from six candidate genes involved in (1) Renin-Angiotensin system: Angiotensin converting enzyme (ACE I/D), (2) Lipid metabolism: Cholesterol Ester Transfer Protein gene (CETP TAQ1B), (3) Platelet aggregation: alpha and beta subunits of the platelet GpIIb/GpIIIa integrin complex (GpIIb HPA3 and GpIIIa Pl(A1/A2)), (4) Coagulation fibrinolysis: Plasminogen Activator Tissue (PLAT TPA25 I/D) and Methylenetetrahydrofolate Reductase (MTHFR C677T and A1298C). The samples were genotyped using the polymerase chain reaction followed by restriction enzyme analysis for the RFLPs. No significant difference in allele frequencies between patient and control groups was observed. The occurrence of the MTHFR T677T genotype and of the T677T/A1298A compound genotype is higher in cases (20%) than in the controls (4%). Odds ratio seems to indicate that individuals with the MTHFR T677T genotype and the T677T/A1298A compound genotype had a 6-fold increased risk for developing CAD (ORs = 6; 95% CIs = 1.96-18.28) suggesting a possible association of MTHFR C677T with the risk of CAD in Corsican population.


Subject(s)
Coronary Artery Disease/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Adult , Biomarkers , Female , France , Gene Dosage , Humans , Male , Middle Aged , Risk Factors
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