title: Combined immunodeficiency due to a homozygous mutation in ORAI1 that deletes the C-terminus that interacts with STIM 1.
abstract: ORAI1 is the pore-forming subunit of the calcium release-activated calcium channel responsible for calcium influx into cells triggered by endoplasmic reticulum store depletion. We report here a patient with severe combined immunodeficiency and absent store-operated calcium entry due to a novel mutation in ORAI1 that results in the expression of a C-terminally truncated protein that abolishes ORAI1 binding to STIM1.
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Yousef R
authors.initials: YR
authors.lastname: Badran
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Massaad
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Bainter
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Brittney
authors.initials: B
authors.lastname: Cangemi
authors.affiliation: Department of Pediatrics, Sultan Qaboos University, Muscat, Oman.
authors.forename: Shafiq Ur Rehman
authors.initials: SU
authors.lastname: Naseem
authors.affiliation: Department of Pediatrics, Sultan Qaboos University, Muscat, Oman.
authors.forename: Hashim
authors.initials: H
authors.lastname: Javad
authors.affiliation: Department of Pediatrics, Sultan Qaboos University, Muscat, Oman.
authors.forename: Salem
authors.initials: S
authors.lastname: Al-Tamemi
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: raif.geha@childrens.harvard.edu.
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Chou
mesh_terms: D001483:Base Sequence; D059472:Exome / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D057809:HEK293 Cells; D006720:Homozygote; D006801:Humans; D007223:Infant; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D000071740:ORAI1 Protein / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1
keywords: ORAI1; Severe combined immunodeficiency; Whole exome sequencing