| 1. |
- Hedberg, Carola, 1969, et al.
(författare)
-
Childhood onset tubular aggregate myopathy associated with de novo STIM1 mutations
- 2014
-
Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 261:5, s. 870-876
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated three unrelated patients with tubular-aggregate myopathy and slowly progressive muscle weakness manifesting in the first years of life. All patients showed type 1 muscle fiber predominance and hypotrophy of type 2 fibers. Tubular aggregates were abundant. In all three patients mutations were identified in the gene STIM1, and the mutations were found to be de novo in all patients. In one of the patients the mutation was identified by exome sequencing. Two patients harbored the previously described mutation c.326A > G p.(His109Arg), while the third patient had a novel mutation c.343A > T p.(Ile115Phe). Taking our series together with previously published cases, the c.326A > G p.(His109Arg) seems to be a hotspot mutation that is characteristically related to early onset muscle weakness.
|
|
| 2. |
- Peca, Donatella, et al.
(författare)
-
Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations
- 2015
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 23:8, s. 1033-1041
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic defects of surfactant metabolism are associated with a broad range of clinical manifestations, from neonatal respiratory distress syndrome to adult interstitial lung disease. Early therapies may improve symptoms but diagnosis is often delayed owing to phenotype and genotype variability. Our objective was to characterize the cellular/ultrastructural correlates of surfactant protein C (SP-C) mutations in children with idiopathic diffuse lung diseases. We sequenced SFTPC - the gene encoding SP-C - SFTPB and ABCA3, and analyzed morphology, ultrastructure and SP expression in lung tissue when available. We identified eight subjects who were heterozygous for SP-C mutations. Median age at onset and clinical course were variable. None of the mutations were located in the mature peptide-encoding region, but were either in the pro-protein BRICHOS or linker C-terminal domains. Although lung morphology was similar to other genetic surfactant metabolism disorders, electron microscopy studies showed specific anomalies, suggesting surfactant homeostasis disruption, plus trafficking defects in the four subjects with linker domain mutation and protein misfolding in the single BRICHOS mutation carrier in whom material was available. Immunolabeling studies showed increased proSP-C staining in all cases. In two cases, amyloid deposits could be identified. Immunochemistry and ultrastructural studies may be useful for diagnostic purposes and for genotype interpretation.
|
|
