Abstract
Calcium (Ca2+) acts as a ubiquitous second messenger, and normal cell and tissue physiology strictly depends on the precise regulation of Ca2+ entry, storage, and release. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling extracellular Ca2+ entry, and mainly relies on the accurate interplay between the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Mutations in STIM1 or ORAI1 result in abnormal Ca2+ homeostasis and are associated with severe human disorders. Recessive loss-of-function mutations impair SOCE and cause combined immunodeficiency, while dominant gain-of-function mutations induce excessive extracellular Ca2+ entry and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). TAM and STRMK are spectra of the same multisystemic disease characterized by muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. To date, 42 TAM/STRMK families have been described, and here we report five additional families for which we provide clinical, histological, ultrastructural, and genetic data. In this study, we list and review all new and previously reported STIM1 and ORAI1 cases, discuss the pathomechanisms of the mutations based on the known functions and the protein structure of STIM1 and ORAI1, draw a genotype/phenotype correlation, and delineate an efficient screening strategy for the molecular diagnosis of TAM/STRMK.
| Original language | English |
|---|---|
| Journal | Human Mutation |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2019 |
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Keywords
- ORAI1
- STIM1
- store-operated calcium entry
- Stormorken syndrome
- tubular aggregate myopathy
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
Tubular aggregate myopathy and Stormorken syndrome : Mutation spectrum and genotype/phenotype correlation. / Morin, Gilles; Biancalana, Valérie; Echaniz-Laguna, Andoni; Noury, Jean Baptiste; Lornage, Xavière; Moggio, Maurizio; Ripolone, Michela; Violano, Raffaella; Marcorelles, Pascale; Maréchal, Denis; Renaud, Florence; Maurage, Claude Alain; Tard, Céline; Cuisset, Jean Marie; Laporte, Jocelyn; Böhm, Johann.
In: Human Mutation, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tubular aggregate myopathy and Stormorken syndrome
T2 - Mutation spectrum and genotype/phenotype correlation
AU - Morin, Gilles
AU - Biancalana, Valérie
AU - Echaniz-Laguna, Andoni
AU - Noury, Jean Baptiste
AU - Lornage, Xavière
AU - Moggio, Maurizio
AU - Ripolone, Michela
AU - Violano, Raffaella
AU - Marcorelles, Pascale
AU - Maréchal, Denis
AU - Renaud, Florence
AU - Maurage, Claude Alain
AU - Tard, Céline
AU - Cuisset, Jean Marie
AU - Laporte, Jocelyn
AU - Böhm, Johann
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Calcium (Ca2+) acts as a ubiquitous second messenger, and normal cell and tissue physiology strictly depends on the precise regulation of Ca2+ entry, storage, and release. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling extracellular Ca2+ entry, and mainly relies on the accurate interplay between the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Mutations in STIM1 or ORAI1 result in abnormal Ca2+ homeostasis and are associated with severe human disorders. Recessive loss-of-function mutations impair SOCE and cause combined immunodeficiency, while dominant gain-of-function mutations induce excessive extracellular Ca2+ entry and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). TAM and STRMK are spectra of the same multisystemic disease characterized by muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. To date, 42 TAM/STRMK families have been described, and here we report five additional families for which we provide clinical, histological, ultrastructural, and genetic data. In this study, we list and review all new and previously reported STIM1 and ORAI1 cases, discuss the pathomechanisms of the mutations based on the known functions and the protein structure of STIM1 and ORAI1, draw a genotype/phenotype correlation, and delineate an efficient screening strategy for the molecular diagnosis of TAM/STRMK.
AB - Calcium (Ca2+) acts as a ubiquitous second messenger, and normal cell and tissue physiology strictly depends on the precise regulation of Ca2+ entry, storage, and release. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling extracellular Ca2+ entry, and mainly relies on the accurate interplay between the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Mutations in STIM1 or ORAI1 result in abnormal Ca2+ homeostasis and are associated with severe human disorders. Recessive loss-of-function mutations impair SOCE and cause combined immunodeficiency, while dominant gain-of-function mutations induce excessive extracellular Ca2+ entry and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). TAM and STRMK are spectra of the same multisystemic disease characterized by muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. To date, 42 TAM/STRMK families have been described, and here we report five additional families for which we provide clinical, histological, ultrastructural, and genetic data. In this study, we list and review all new and previously reported STIM1 and ORAI1 cases, discuss the pathomechanisms of the mutations based on the known functions and the protein structure of STIM1 and ORAI1, draw a genotype/phenotype correlation, and delineate an efficient screening strategy for the molecular diagnosis of TAM/STRMK.
KW - ORAI1
KW - STIM1
KW - store-operated calcium entry
KW - Stormorken syndrome
KW - tubular aggregate myopathy
UR - http://www.scopus.com/inward/record.url?scp=85073993761&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073993761&partnerID=8YFLogxK
U2 - 10.1002/humu.23899
DO - 10.1002/humu.23899
M3 - Article
C2 - 31448844
AN - SCOPUS:85073993761
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
ER -