Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
Clin Genet ; 91(5): 780-786, 2017 May.
Article in English | MEDLINE | ID: mdl-27882542

ABSTRACT

We present three members of an Italian family affected by tubular aggregate myopathy (TAM) and congenital miosis harboring a novel missense mutation in ORAI1. All patients had a mild, late onset TAM revealed by asymptomatic creatine kinase (CK) elevation and congenital miosis consistent with a Stormorken-like Syndrome, in the absence of thrombocytopathy. Muscle biopsies showed classical histological findings but ultrastructural analysis revealed atypical tubular aggregates (TAs). The whole body muscle magnetic resonance imaging (MRI) showed a similar pattern of muscle involvement that correlated with clinical severity. The lower limbs were more severely affected than the scapular girdle, and thighs were more affected than legs. Molecular analysis revealed a novel c.290C>G (p.S97C) mutation in ORAI1 in all affected patients. Functional assays in both human embryonic kidney (HEK) cells and myotubes showed an increased rate of Ca2+ entry due to a constitutive activation of the CRAC channel, consistent with a 'gain-of-function' mutation. In conclusion, we describe an Italian family harboring a novel heterozygous c.290C>G (p.S97C) mutation in ORAI1 causing a mild- and late-onset TAM and congenital miosis via constitutive activation of the CRAC channel. Our findings extend the clinical and genetic spectrum of the ORAI1-related TAM.


Subject(s)
Mutation , Myopathies, Structural, Congenital/genetics , ORAI1 Protein/genetics , Pupil Disorders/congenital , Age of Onset , Calcium Release Activated Calcium Channels/metabolism , Female , Heterozygote , Humans , Male , Middle Aged , Myopathies, Structural, Congenital/physiopathology , ORAI1 Protein/metabolism , Pedigree , Pupil Disorders/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...