Complex phenotypes associated with STIM1 mutations in both coiled coil and EF-hand domains.
Neuromuscul Disord
; 27(9): 861-872, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28624464
ABSTRACT
Dominant mutations in STIM1 are a cause of three allelic conditions tubular aggregate myopathy, Stormorken syndrome (a complex phenotype including myopathy, hyposplenism, hypocalcaemia and bleeding diathesis), and a platelet dysfunction disorder, York platelet syndrome. Previous reports have suggested a genotype-phenotype correlation with mutations in the N-terminal EF-hand domain associated with tubular aggregate myopathy, and a common mutation at p.R304W in a coiled coil domain associated with Stormorken syndrome. In this study individuals with STIM1 variants were identified by exome sequencing or STIM1 direct sequencing, and assessed for neuromuscular, haematological and biochemical evidence of the allelic disorders of STIM1. STIM1 mutations were investigated by fibroblast calcium imaging and 3D modelling. Six individuals with STIM1 mutations, including two novel mutations (c.262A>G (p.S88G) and c.911G>A (p.R304Q)), were identified. Extra-neuromuscular symptoms including thrombocytopenia, platelet dysfunction, hypocalcaemia or hyposplenism were present in 5/6 patients with mutations in both the EF-hand and CC domains. 3/6 patients had psychiatric disorders, not previously reported in STIM1 disease. Review of published STIM1 patients (n = 49) confirmed that neuromuscular symptoms are present in most patients. We conclude that the phenotype associated with activating STIM1 mutations frequently includes extra-neuromuscular features such as hypocalcaemia, hypo-/asplenia and platelet dysfunction regardless of mutation domain.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Baço
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Transtornos Plaquetários
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Miose
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Miopatias Congênitas Estruturais
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Dislexia
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Estudos de Associação Genética
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Molécula 1 de Interação Estromal
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Ictiose
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Transtornos de Enxaqueca
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Mutação
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neuromuscul Disord
Ano de publicação:
2017
Tipo de documento:
Article