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Novel phenotype in STIM1-related disorders including bones abnormalities and absence of immune defect

Abstract : STIM1, the stromal interaction molecule 1, is the key protein for maintaining calcium concentration in the endoplasmic reticulum by triggering the Store Operated Calcium Entry (SOCE). Bi-allelic mutations in STIM1 gene are responsible for a loss of STIM1 function in patients affected with a CRAC channelopathy syndrome in which severe combined immunodeficiency syndrome, autoimmunity, ectodermal dysplasia and muscle hypotonia are combined. Here, we studied two siblings from a consanguineous Syrian family, presenting with muscle weakness, hyperlaxity, elastic skin and tooth abnormalities, but no immune disorders. Patients presented with bones abnormalities such as dysmorphic facies and hypoplastic patellae. Using exome sequencing, we have identified a new homozygous frameshift mutation in STIM1: c.685delT [p.(Phe229Leufs*12)], leading to a complete loss of the full-length STIM1 protein. In this study we describe a new phenotype linked to STIM1 mutations. This is to our knowledge, the first description of the involvement of STIM1 causing bone abnormalities. Moreover, we show that the complete loss of STIM1 function is not always associated with immune disorders. Altogether our results broaden the spectrum of phenotypes associated with mutations in STIM1 and opens new perspectives on the pathological mechanisms associated with a defect in the proteins constituting the SOCE complex
Keywords : CRAC STIM1 Muscles SOCE
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Contributor : Marc Bartoli <>
Submitted on : Monday, March 29, 2021 - 2:52:00 PM
Last modification on : Thursday, April 1, 2021 - 6:40:34 PM

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Alexandra Salvi, Skrypnyk Cristina, Nathalie da Silva, Jon Andoni Urtizberea, Bakhiet Moiz, et al.. Novel phenotype in STIM1-related disorders including bones abnormalities and absence of immune defect. Clinical Genetics, Wiley, In press. ⟨hal-03184458⟩

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