Gaucher disease: Biochemical and molecular findings in 141 patients diagnosed in Greece.
ABSTRACT: Highlights•Gaucher disease in Greece has an incidence estimate of 2.8/100,000 births.•Mutation analysis in 125 patients identified 28 different mutations and 37 different genotypes.•Seven of the mutations were not previously reported: T231I, D283N, N462Y, LI75P, F81L, Y135S and T482K.•Mutation D409H;H255Q was only identified in Greek and Albanian patients.
Project description:Gaucher disease results, in most patients, from mutations in the gene encoding glucocerebrosidase. Mutation D409H is the third most frequent in Spanish patients, accounting for 5.7% of all mutated alleles. This allele is associated mainly with the neurological forms of the disease. Recently, homozygosity for the D409H mutation has been associated with a particular phenotype, including specific cardiovascular symptoms. Here we report a second Spanish patient bearing the D409H/D409H genotype with a very early manifestation of the disease. The patient started enzyme replacement therapy at 3 months of age. A common origin for the Spanish D409H alleles was ruled out by haplotype analysis using an internal polymorphism of the glucocerebrosidase gene and two external microsatellite markers.
Project description:Gaucher disease is an autosomal recessively inherited disease caused by mutations at the acid beta-glucosidase (GCase) locus (GBA). To develop viable models of Gaucher disease, point mutations (pmuts), encoding N370S, V394L, D409H, or D409V were introduced into the mouse GCase (gba) locus. DNA sequencing verified each unique pmut. Mutant GCase mRNAs were near wild-type (WT) levels. GCase activities were reduced to 2 to 25% of WT in liver, lung, spleen, and cultured fibroblasts from pmut/pmut or pmut/null mice. The corresponding brain GCase activities were approximately 25% of WT. N370S homozygosity was lethal in the neonatal period. For the other pmut mice, a few storage cells appeared in the spleen at > or =7 months (D409H or D409V homozygotes) or > or =1 year (V394L homozygotes). V394L/null, D409H/null, or D409V/null mice showed scattered storage cells in spleen at approximately 3 to 4 months. Occasional storage cells (sinusoidal cells) were present in liver. In D409V/null mice, large numbers of Mac-3-positive storage cells (ie, macrophages) accumulated in the lung. Glycosphingolipid analyses showed varying rates of progressive glucosylceramide accumulation in visceral organs of pmut/pmut or pmut/null mice, but not in brain. These GCase-deficient mice provide tools for gaining insight into the pathophysiology of Gaucher disease and developing improved therapies.
Project description:Gaucher disease is the most common sphingolipid storage disease and is present in all ethnic groups. Its symptoms span all systems including the cardiovascular system. The health care provider should be vigilant regarding this potentially fatal complication. Gaucher disease type IIIC has been linked to causing oculomotor apraxia and cardiac calcification. We report a Saudi girl who developed valvular and aortic calcification in late childhood and died as a result of her cardiovascular complications. This report further strengthens the association and reminds the clinicians that patients with D409H mutation need echocardiographic evaluation annually.
Project description:The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients.To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients.A review of data in SpRGD from patients' diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (≤1994, cohort A; ≥1995, cohort B).A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17-16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed ≤ 1994 and 53 ≥ 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p < 0.001) and different between the subtypes, GD1: 8.2 (0.2-16.5) years and GD3: 2.8 (0.17-10.2) years (p < 0.001). There were more severe patients in the group diagnosed before 1994 (p = 0.045) carrying L444P (2), D409H (2), G377S (1), G195W (1) or the recombinant mutation. The patients' diagnosed ≤1994 showed worse cytopenias, higher chance of bone vascular complications at diagnosis and previous spleen removal. The patients started ERT at a median time after diagnosis of 5.2 years [cohort A] and 1.6 years [cohort B] (p < 0.001).The early diagnosis of Gaucher disease in the era of ERT availability has permitted to reduce the incidence of severe and irreversible initial complication in pediatric patients, and this has permitted better development of these patients. This is the largest pediatric cohort from a national registry.
Project description:Gaucher disease, a prevalent lysosomal storage disease, is caused by insufficient activity of acid ?-glucosidase (GCase) and resultant glucosylceramide accumulation. Recently in Parkinson disease (PD) patients, heterozygous mutations in GCase have been associated with earlier onset and more progressive PD. To understand the pathogenic relationships between GCase variants and Parkinsonism, ?-synuclein and ubiquitin distributions and levels in the brains of several mouse models containing GCase variants were evaluated by immunohistochemistry. Progressive ?-synuclein and ubiquitin aggregate accumulations were observed in the cortex, hippocampus, basal ganglia, brainstem, and some cerebellar regions between 4 and 24 weeks in mice that were homozygous for GCase [D409H (9H) or V394L (4L)] variants and also had a prosaposin hypomorphic (PS-NA) transgene. In 4L/PS-NA and 9H/PS-NA mice, this was coincident with progressive neurological manifestations and brain glucosylceramide accumulation. Ultrastructural studies showed electron dense inclusion bodies in neurons and axons of 9H/PS-NA brains. ?-synuclein aggregates were also observed in ventricular, brainstem, and cerebellar regions of older mice (>42-weeks) with the GCase variant (D409H/D409H) without overt neurological disease. In a chemically induced GCase deficiency, ?-synuclein aggregates and glucosylceramide accumulation also occurred. These studies demonstrate a relationship between glucosylceramide accumulation and ?-synuclein aggregates, and implicate glucosylceramide accumulation as risk factor for the ?-synucleinopathies.
Project description:We employed mtDNA and nuclear SNPs to investigate the genetic diversity of sheep breeds of three countries of the Mediterranean basin: Albania, Greece, and Italy. In total, 154 unique mtDNA haplotypes were detected by means of D-loop sequence analysis. The major nucleotide diversity was observed in Albania. We identified haplogroups, A, B, and C in Albanian and Greek samples, while Italian individuals clustered in groups A and B. In general, the data show a pattern reflecting old migrations that occurred in postneolithic and historical times. PCA analysis on SNP data differentiated breeds with good correspondence to geographical locations. This could reflect geographical isolation, selection operated by local sheep farmers, and different flock management and breed admixture that occurred in the last centuries.
Project description:The checklist of Greek Cyanobacteria was created in the framework of the Greek Taxon Information System (GTIS), an initiative of the LifeWatchGreece Research Infrastructure (ESFRI) that has resumed efforts to compile a complete checklist of species reported from Greece. This list was created from exhaustive search of the scientific literature of the last 60 years. All records of taxa known to occur in Greece were taxonomically updated.The checklist of Greek Cyanobacteria comprises 543 species, classified in 130 genera, 41 families, and 8 orders. The orders Synechococcales and Oscillatoriales have the highest number of species (158 and 153 species, respectively), whereas these two orders along with Nostocales and Chroococcales cover 93% of the known Greek cyanobacteria species. It is worth mentioning that 18 species have been initially described from Greek habitats. The marine epilithic Ammatoidea aegea described from Saronikos Gulf is considered endemic to this area. Our bibliographic review shows that Greece hosts a high diversity of cyanobacteria, suggesting that the Mediterranean area is also a hot spot for microbes.
Project description:The first attempt to compile the checklist of Cumacea of Greece was made in the context of the "Greek Biodiversity Database" project (2005-2008) coordinated by the Aristotle University of Thessaloniki. Since then, only scattered information on new elements of the Greek cumacean fauna has been available. The objectives of the present study were to update and cross-check taxonomically all cumacean species records from Greek waters for inaccuracies and omissions according to the recent literature and current taxonomic status.The updated checklist of Cumacea of Greece, which was built within the framework of the LifeWatch Greece Research Infrastructure (ESFRI) project (2013-2015) coordinated by the Hellenic Centre for Marine Research, comprises 62 species, classified in 24 genera and 6 families. However, a few more records need further cross-checking with the current literature resources.
Project description:BACKGROUND:SNP data of goats of three Mediterranean countries were used for population studies and reconstruction of geographical patterning. 496 individuals belonging to Italian, Albanian and Greek breeds were genotyped to assess the basic population parameters. RESULTS:A total of 26 SNPs were used, for a total of 12,896 genotypes assayed. Statistical analysis revealed that breeds are not so similar in terms of genetic variability, as reported in studies performed using different markers. The Mantel test showed a strongly significant correlation between genetic and geographic distance. Also, PCA analysis revealed that breeds are grouped according to geographical origin, with the exception of the Greek Skopelos breed. CONCLUSION:Our data point out that the use of SNP markers to analyze a wider breed sample could help in understanding the recent evolutionary history of domestic goats. We found correlation between genetic diversity and geographic distance. Also PCA analysis shows that the breeds are well differentiated, with good correspondence to geographical locations, thus confirming the correlation between geographical and genetic distances. This suggests that migration history of the species played a pivotal role in the present-day structure of the breeds and a scenario in which coastal routes were easier for migrating in comparison with inland routes. A westward coastal route to Italy through Greece could have led to gene flow along the Northern Mediterranean.
Project description:The checklist of Porifera of Greece was created in the framework of the Greek Taxon Information System (GTIS), an initiative of the LifeWatchGreece Research Infrastructure (ESFRI) that has resumed efforts to compile a complete checklist of species recorded from Greece. An updated checklist of Porifera was created on the basis of a list of the Aegean Demospongiae and Homoscleromorpha published one decade ago. All records of species known to occur in Greek waters were taxonomically validated and cross-checked for possible inaccuracies and omissions. Then, all recent publications were reviewed and the species recorded from 2006 to date were added to the list.The updated checklist of Porifera of Greece comprises 215 species, classified to 111 genera, 65 families, 24 orders, and 4 classes. In total, 34 new additions were made to the previous species list (8 Calcarea, 17 Demospongiae, 1 Hexactinellida, and 6 Homoscleromorpha) with Calcarea being listed for the first time from the area. The demosponge orders Poecilosclerida, Dictyoceratida, Tetractinellida, Haplosclerida, and Suberitida have the highest number of species covering 62% of the known Greek sponge species richness. It is worth mentioning that 8 species have been first described from Greek waters, 7 of which are considered endemic to this area. Our bibliographic overview also revealed knowledge gaps with regard to specific habitats typically rich in sponge diversity, and marine sectors of Greece.