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| Osteogenesis imperfecta v1.19 | SEC24D | Duncan Baker reviewed gene: SEC24D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.19 | CREB3L1 | Duncan Baker edited their review of gene: CREB3L1: Added comment: Following discussion with Dr Balasubramanian - rate green. PMID: 29936144 Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta. A homozygous CREB3L1 stop codon mutation in a boy with severe OI, had blue sclera and tooth agenesis. Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%); however, collagen I levels were only reduced in hOBs (5-10%). Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to life-long bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures. PMID: 30657919 A homozygous pathogenic missense variant broadens the phenotypic and mutational spectrum of CREB3L1-related osteogenesis imperfecta. Identified the first homozygous pathogenic missense variant (p.(Ala304Val)) in a patient with lethal OI, which is located within the highly conserved basic leucine zipper domain, four amino acids upstream of the DNA binding domain. In vitro structural modeling and luciferase assays demonstrate that this missense variant affects a critical residue in this functional domain, thereby decreasing the type I collagen transcriptional binding ability. In addition, overexpression of the mutant OASIS protein leads to decreased transcription of the SEC23A and SEC24D genes, which code for components of the coat protein complex type II (COPII), and aberrant OASIS signaling also results in decreased protein levels of SEC24D.; Changed publications: 29936144, 30657919; Changed phenotypes: Osteogenesis imperfecta, type XVI 616229 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.18 | SEC24D | Eleanor Williams reviewed gene: SEC24D: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.17 | SEC24D |
Eleanor Williams Source NHS GMS was added to SEC24D. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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