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Query: UMLS:C0029089 (
ophthalmoplegia
)
3,338
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tubular aggregates in human muscle biopsies have been reported to occur in a variety of acquired and hereditary neuromuscular conditions since 1964. Recently mutations in the gene encoding the main calcium sensor in the sarcoplasmic reticulum,
stromal interaction molecule 1
(
STIM1
), have been identified as a cause of autosomal dominant tubular aggregate myopathy. We studied a German family with tubular aggregate myopathy and defined cellular consequences of altered
STIM1
function. Both patients in our family had early progressive myopathy with proximal paresis of arm and leg muscles, scapular winging, ventilatory failure, joint contractures and external
ophthalmoplegia
. One patient had a well-documented disease course over 50 years. Sequencing of the
STIM1
gene revealed a previously unreported missense mutation (c.242G>A; p.Gly81Asp) located in the first calcium binding EF domain. Functional characterization of the new
STIM1
mutation by calcium imaging revealed that calcium influx was significantly increased in primary myoblasts of the index patient compared to controls pointing at a severe alteration of intracellular calcium homeostasis. This new family widens the spectrum of
STIM1
-associated myopathies to a more severe phenotype.
...
PMID:50 years to diagnosis: Autosomal dominant tubular aggregate myopathy caused by a novel STIM1 mutation. 2595 20
STIM1
is a reticular Ca
2+
sensor composed of a luminal and a cytosolic domain. Missense mutations in the luminal domain have been associated with tubular aggregate myopathy (TAM), while cytosolic mutations can cause Stormorken syndrome, a multisystemic disease associating TAM with asplenia, thrombocytopenia, miosis, ichthyosis, short stature and dyslexia. Here we present the case of a 41-year-old female complaining of exercise intolerance. Clinical examination showed short stature, scoliosis, proximal muscle weakness with lower limb predominance, and
ophthalmoplegia
. Laboratory tests revealed hypocalcemia, mild anemia and elevated creatine kinase (CK) levels. Whole-body muscle magnetic resonance imaging (MRI) revealed asplenia. Muscle biopsy was consistent with TAM.
STIM1
gene analysis disclosed the novel c.252T>A, p.D84E missense mutation which was shown to induce constitutive
STIM1
clustering in a functional study. This study reports a novel
STIM1
mutation located in the Ca
2+
-binding EF domain causing TAM with features of Stormorken syndrome.
...
PMID:Tubular aggregate myopathy with features of Stormorken disease due to a new STIM1 mutation. 2787 57
