Deficiency for the ER-stress transducer OASIS causes severe recessive osteogenesis imperfecta in humans.
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous brittle bone disorder. Whereas dominant OI is mostly due to heterozygous mutations in either COL1A1 or COL1A2, encoding type I procollagen, recessive OI is caused by biallelic mutations in genes encoding proteins involved in type I procollagen processing or chaperoning. Hitherto, some OI cases remain molecularly unexplained. We detected a homozygous genomic deletion of CREB3L1 in a family with severe OI. CREB3L1 encodes OASIS, an endoplasmic reticulum-stress transducer that regulates type I procollagen expression during murine bone formation. This is the first report linking CREB3L1 to human recessive OI, thereby expanding the OI gene spectrum.
Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium. Paul.Coucke@UGent.be.
Sofie
S
Symoens
Fransiska
F
Malfait
Sanne
S
D'hondt
Bert
B
Callewaert
Annelies
A
Dheedene
Wouter
W
Steyaert
Hans Peter
HP
Bächinger
Anne
A
De Paepe
Hulya
H
Kayserili
Paul J
PJ
Coucke
D024042:Collagen Type I / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy
C485618:CREB3L1 protein, human; D024042:Collagen Type I; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins