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- Smol, T., et al.
(författare)
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MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype
- 2018
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Ingår i: Neurogenetics. - : SPRINGER. - 1364-6745 .- 1364-6753. ; 19:2, s. 93-103
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Tidskriftsartikel (refereegranskat)abstract
- Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.
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| 2. |
- Lundholm, N., et al.
(författare)
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Induction of domoic acid production in diatoms-Types of grazers and diatoms are important
- 2018
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Ingår i: Harmful Algae. - : Elsevier BV. - 1568-9883. ; 79, s. 64-73
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Tidskriftsartikel (refereegranskat)abstract
- Grazers can induce toxin (domoic acid, DA) production in diatoms. The toxic response has been observed in two species of Pseudo-nitzschia and was induced by Calanus copepods. In this study, interactions between diatoms and copepods were further explored using different species of diatoms and copepods. All herbivorous copepods induced toxin production, whereas exposure to carnivorous copepods did not. In line with this, increasing the number of herbivorous copepods resulted in even higher toxin production. The induced response is thus only elicited by copepods that pose a real threat to the responding cells, which supports that the induced toxin production in diatoms evolved as an inducible defense. The cellular toxin content in Pseudo-nitzschia was positively correlated to the concentration of a group of specific polar lipids called copepodamides that are excreted by the copepods. This suggests that copepodamides are the chemical cues responsible for triggering the toxin production. Carnivorous copepods were found to produce less or no copepodamides. Among the diatoms exposed to grazing herbivorous copepods, only two of six species of Pseudo-nitzschia and none of the Nitzschia or Fragilariopsis strains responded by producing DA, indicating that not all Pseudo-nitzschia species/strains are able to produce DA, and that different diatom species might have different strategies for coping with grazing pressure. Growth rate was negatively correlated to cellular domoic acid content indicating an allocation cost associated with toxin production. Long-term grazing experiments showed higher mortality rates of grazers fed toxic diatoms, supporting the hypothesis that DA production is an induced defense mechanism.
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