| 1. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 2. |
- Mehrtens, Nicola, et al.
(författare)
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The XMM Cluster Survey : optical analysis methodology and the first data release
- 2012
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 423:2, s. 1024-1052
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Tidskriftsartikel (refereegranskat)abstract
- The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMMNewton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we present the first data release from the XMM Cluster Survey (XCS-DR1). This consists of 503 optically confirmed, serendipitously detected, X-ray clusters. Of these clusters, 256 are new to the literature and 357 are new X-ray discoveries. We present 463 clusters with a redshift estimate (0.06 < z < 1.46), including 261 clusters with spectroscopic redshifts. The remainder have photometric redshifts. In addition, we have measured X-ray temperatures (TX) for 401 clusters (0.4 < TX < 14.7 keV). We highlight seven interesting subsamples of XCS-DR1 clusters: (i) 10 clusters at high redshift (z > 1.0, including a new spectroscopically confirmed cluster at z= 1.01); (ii) 66 clusters with high TX (>5 keV); (iii) 130 clusters/groups with low TX (<2 keV); (iv) 27 clusters with measured TX values in the Sloan Digital Sky Survey (SDSS) Stripe 82 co-add region; (v) 77 clusters with measured TX values in the Dark Energy Survey region; (vi) 40 clusters detected with sufficient counts to permit mass measurements (under the assumption of hydrostatic equilibrium); (vii) 104 clusters that can be used for applications such as the derivation of cosmological parameters and the measurement of cluster scaling relations. The X-ray analysis methodology used to construct and analyse the XCS-DR1 cluster sample has been presented in a companion paper, Lloyd-Davies et al.
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| 3. |
- Johnstone, Devon L., et al.
(författare)
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Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ : Report of seven new subjects and review of the literature
- 2020
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 43:6, s. 1321-1332
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Tidskriftsartikel (refereegranskat)abstract
- We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants in PIGQ.
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| 4. |
- Shah, Rameen, et al.
(författare)
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ALG13-Congenital Disorder of Glycosylation (ALG13-CDG) : Updated clinical and molecular review and clinical management guidelines
- 2024
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Ingår i: Molecular Genetics and Metabolism. - 1096-7192. ; 142:2
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Forskningsöversikt (refereegranskat)abstract
- ALG13-Congenital Disorder of Glycosylation (CDG), is a rare X-linked CDG caused by pathogenic variants in ALG13 (OMIM 300776) that affects the N-linked glycosylation pathway. Affected individuals present with a predominantly neurological manifestation during infancy. Epileptic spasms are a common presenting symptom of ALG13-CDG. Other common phenotypes include developmental delay, seizures, intellectual disability, microcephaly, and hypotonia. Current management of ALG13-CDG is targeted to address patients’ symptoms. To date, less than 100 individuals have been reported with ALG13-CDG. In this article, an international group of experts in CDG reviewed all reported individuals affected with ALG13-CDG and suggested diagnostic and management guidelines for ALG13-CDG. The guidelines are based on the best available data and expert opinion. Neurological symptoms dominate the phenotype of ALG13-CDG where epileptic spasm is confirmed to be the most common presenting symptom of ALG13-CDG in association with hypotonia and developmental delay. We propose that ACTH/prednisolone treatment should be trialed first, followed by vigabatrin, however ketogenic diet has been shown to have promising results in ALG13-CDG. In order to optimize medical management, we also suggest early cardiac, gastrointestinal, skeletal, and behavioral assessments in affected patients.
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