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- Stray-Pedersen, Asbjorg, et al.
(författare)
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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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| 3. |
- Wang, Zhongli, et al.
(författare)
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Prevalence and associated metabolic factors of fatty liver disease in the elderly
- 2013
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 48:8, s. 705-709
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the metabolic risk factors for fatty liver disease in the elderly, and determine the prevalence of fatty liver disease in the elderly in Wuhan, central China.METHODS: The study was a case-control study based on all 4226 adults above 60years of age from a cohort investigated in 2010-11 at the medical examination center of Zhongnan hospital, using 3145 randomly selected adults under 60years of age from the same cohort as controls. Fatty liver disease (FLD) was identified with ultrasound imaging. The risk factors measured were body mass index (BMI), and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low density lipoprotein (LDL) and serum uric acid (SUA). The probability of steatohepatitis with advanced fibrosis was predicted using a score based on BMI, age, ALT, and TG (BAAT),and using AST/ALT ratio (AAR).RESULTS: FLD was higher in the elderly (26.7%) than in the non-elderly (22.8%) and similar in the elderly between men and women (26.6% vs 27.0%, p>0.05). BMI, TC, TG, LDL, SUA, AST and ALT were all significantly higher in FLD, whereas the level of HDL was markedly lower. Multiple regression analyses showed that obesity, high TC, TG, SUA, low HDL, and elevated ALT, AAR<1 were closely related to the elderly FLD, while male sex, obesity, high TC, TG, low HDL, elevated ALT, AST and AAR<1 were closely related to the non-elderly FLD. The prevalence of steatohepatitis with advanced fibrosis estimated as BAAT index≥3 was 2.4% in all subjects, and was higher in the elderly FLD patients than in the non-elderly FLD patients.CONCLUSION: The prevalence of FLD is higher in the elderly, and is broadly related to the same metabolic risk factors as in the non-elderly. However, female-sex is no longer protective with increasing age, and the prevalence of steatohepatitis with advanced fibrosis is estimated to be considerably higher in the elderly FLD patients than in the non-elderly FLD controls.
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