Morin, Gilles, Bruechle, Nadina Ortiz, Singh, Amrathlal Rabbind, Knopp, Cordula, Jedraszak, Guillaume, Elbracht, Miriam, Bremond-Gignac, Dominique, Hartmann, Kathi, Sevestre, Henri, Deutz, Peter, Herent, Didier, Nuernberg, Peter, Romeo, Bernard, Konrad, Kerstin ORCID: 0000-0001-9039-2615, Mathieu-Dramard, Michele, Oldenburg, Johannes, Bourges-Petit, Elisabeth, Shen, Yuequan, Zerres, Klaus, Ouadid-Ahidouch, Halima and Rochette, Jacques (2014). Gain-of-Function Mutation in STIM1 (P.R304W) Is Associated with Stormorken Syndrome. Hum. Mutat., 35 (10). S. 1221 - 1233. HOBOKEN: WILEY-BLACKWELL. ISSN 1098-1004

Full text not available from this repository.

Abstract

Stormorken syndrome is a rare autosomal dominant disorder characterized by a phenotype that includes miosis, thrombocytopenia/thrombocytopathy with bleeding time diathesis, intellectual disability, mild hypocalcemia, muscle fatigue, asplenia, and ichthyosis. Using targeted sequencing and whole-exome sequencing, we identified the c.910C > T transition in a STIM1 allele (p.R304W) only in patients and not in their unaffected family members. STIM1 encodes stromal interaction molecule 1 protein (STIM1), which is a finely tuned endoplasmic reticulum Ca2+ sensor. The effect of the mutation on the structure of STIM1 was investigated by molecular modeling, and its effect on function was explored by calcium imaging experiments. Results obtained from calcium imaging experiments using transfected cells together with fibroblasts from one patient are in agreement with impairment of calcium homeostasis. We show that the STIM1 p.R304W variant may affect the conformation of the inhibitory helix and unlock the inhibitory state of STIM1. The p.R304W mutation causes a gain of function effect associated with an increase in both resting Ca2+ levels and store-operated calcium entry. Our study provides evidence that Stormorken syndrome may result from a single-gene defect, which is consistent with Mendelian-dominant inheritance.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Morin, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruechle, Nadina OrtizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singh, Amrathlal RabbindUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knopp, CordulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jedraszak, GuillaumeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elbracht, MiriamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bremond-Gignac, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, KathiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sevestre, HenriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deutz, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herent, DidierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romeo, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konrad, KerstinUNSPECIFIEDorcid.org/0000-0001-9039-2615UNSPECIFIED
Mathieu-Dramard, MicheleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oldenburg, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bourges-Petit, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shen, YuequanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zerres, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ouadid-Ahidouch, HalimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rochette, JacquesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-428066
DOI: 10.1002/humu.22621
Journal or Publication Title: Hum. Mutat.
Volume: 35
Number: 10
Page Range: S. 1221 - 1233
Date: 2014
Publisher: WILEY-BLACKWELL
Place of Publication: HOBOKEN
ISSN: 1098-1004
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PHOSPHOGLYCERATE MUTASE DEFICIENCY; HEREDITARY SYNDROME; BLEEDING TENDENCY; SKELETAL-MUSCLE; GYRATE ATROPHY; EXTREME MIOSIS; MYOPATHY; THROMBOCYTOPATHIA; ENTRY; HYPERORNITHINEMIAMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42806

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item