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- Gkourogianni, Alexandra, et al.
(författare)
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Clinical characterization of patients with autosomal dominant short stature due to aggrecan mutations
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Cary, USA : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 460-469
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Tidskriftsartikel (refereegranskat)abstract
- Context: Heterozygous mutations in the Aggrecan gene (ACAN) cause autosomal dominant short stature with bone age (BA) acceleration, premature growth cessation and minor skeletal abnormalities.Objective: Characterize the phenotypic spectrum, associated conditions and response to growth-promoting therapies.Design: Retrospective international cohort study.Patients: Information from 103 individuals (57 female, 46 male) from 20 families with confirmed heterozygous ACAN mutations were included.Methods: Families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next generation sequencing, and/or Sanger sequencing. Clinical information was collected from medical records.Results: Identified ACAN variants showed perfect co-segregation with phenotype. Adult individuals had mildly disproportionate short stature (median height: -2.8 SDS, range: -5.9 to -0.9) and histories of early growth cessation. The condition was frequently associated with early-onset osteoarthritis (12 families) and intervertebral disc disease (9 families). There was no apparent genotype-phenotype correlation between type of ACAN mutation and presence of joint complaints. During childhood, height was less affected (median height: -2.0 SDS, range: -4.2 to -0.6). In contrast to most children with short stature, the majority of children had advanced BA (BA - CA, median: +1.3y; range +0.0 to +3.7y) reflecting a reduction in remaining growth potential. Nineteen individuals had received GH with some evidence of increased growth velocity.Conclusions Heterozygous ACAN mutations result in a phenotypic spectrum ranging from mild and proportionate short stature to a mild skeletal dysplasia with disproportionate short stature and brachydactyly. In several of the families, affected individuals developed early-onset osteoarthritis and degenerative disc disease requiring intervention, suggesting dysfunction of articular cartilage and intervertebral disc cartilage. Additional studies are needed to determine the optimal treatment strategy for these patients.
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| 2. |
- Steffen, Will, et al.
(författare)
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Stratigraphic and Earth System approaches to defining the Anthropocene
- 2016
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Ingår i: Earth's Future. - 2328-4277. ; 4:8, s. 324-345
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Forskningsöversikt (refereegranskat)abstract
- Stratigraphy provides insights into the evolution and dynamics of the Earth System over its long history. With recent developments in Earth System science, changes in Earth System dynamics can now be observed directly and projected into the near future. An integration of the two approaches provides powerful insights into the nature and significance of contemporary changes to Earth. From both perspectives, the Earth has been pushed out of the Holocene Epoch by human activities, with the mid-20th century a strong candidate for the start date of the Anthropocene, the proposed new epoch in Earth history. Here we explore two contrasting scenarios for the future of the Anthropocene, recognizing that the Earth System has already undergone a substantial transition away from the Holocene state. A rapid shift of societies toward the UN Sustainable Development Goals could stabilize the Earth System in a state with more intense interglacial conditions than in the late Quaternary climate regime and with little further biospheric change. In contrast, a continuation of the present Anthropocene trajectory of growing human pressures will likely lead to biotic impoverishment and a much warmer climate with a significant loss of polar ice.
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