| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Osteogenesis imperfecta v2.27 | COPB2 | Eleanor Williams Publications for gene: COPB2 were set to Marom et al 2018 ASBMR: COPB2 Loss of Function Leads to Disrupted Collagen Trafficking and Juvenile Osteoporosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v2.13 | ICK | Arina Puzriakova Tag curated_removed tag was added to gene: ICK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v2.12 | ICK | Arina Puzriakova Phenotypes for gene: ICK were changed from Disproportionate Short Stature to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v2.6 | MESD |
Eleanor Williams changed review comment from: Gene suggested by Alistair Pagnamenta. Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM. PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking. Sources: Literature; to: Gene suggested by Alistair Pagnamenta. Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM. PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking. Alistair Pagnamenta notes that there is a lack of sibling data. |
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| Osteogenesis imperfecta v2.4 | MESD |
Eleanor Williams gene: MESD was added gene: MESD was added to Osteogenesis imperfecta. Sources: Literature Mode of inheritance for gene: MESD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MESD were set to 31564437 Added comment: Gene suggested by Alistair Pagnamenta. Associated with Osteogenesis imperfecta, type XX, #618644 (AR) in OMIM. PMID: 31564437 Moosa et al 2019. Report 5 independent consanguineous families with a progressively deforming type of OI. Using WES and prioritising homozygous variants, they found all patients were homozygous for a mutation in the third and final exon of MESD. Parents were heterozygous. Variants were not common polymorphisms. 4 different truncation or frameshift variants were found. In mice, homozygous loss-of-function Mesd mutations cause embryonic lethality during gastrulation (PubMed: 11247670). In functional studies the MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking. Sources: Literature |
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| Osteogenesis imperfecta v2.0 | ICK | Eleanor Williams commented on gene: ICK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v2.0 | ICK | Eleanor Williams Tag new-gene-name tag was added to gene: ICK. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.36 | COL11A2 | Eleanor Williams commented on gene: COL11A2: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to keep this gene red as it is associated with Stickler syndrome which is covered by other panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.36 | COL11A1 | Eleanor Williams commented on gene: COL11A1: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04 it was decided to keep this gene red as it is associated with Stickler syndrome which is covered by other panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.34 | COL11A2 | Eleanor Williams Phenotypes for gene: COL11A2 were changed from Disproportionate Short Stature; Stickler Syndrome, Type III to Disproportionate Short Stature; Stickler Syndrome, Type III; Otospondylomegaepiphyseal dysplasia 184840 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.33 | COL11A1 | Eleanor Williams Phenotypes for gene: COL11A1 were changed from Disproportionate Short Stature to Disproportionate Short Stature; ibrochondrogenesis 1228520; Stickler syndrome, type II 604841; Marshall Syndrome 154780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.19 | COL11A1 | Duncan Baker edited their review of gene: COL11A1: Added comment: Following discussion with Dr Balasubramanian - rate green; Changed phenotypes: ibrochondrogenesis 1228520, Stickler syndrome, type II 604841; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v1.16 | COL11A1 | Duncan Baker reviewed gene: COL11A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fibrochondrogenesis 1, Stickler syndrome, type II; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Osteogenesis imperfecta v1.16 | COPB2 |
Duncan Baker gene: COPB2 was added gene: COPB2 was added to Osteogenesis imperfecta. Sources: Expert list Mode of inheritance for gene: COPB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: COPB2 were set to Marom et al 2018 ASBMR: COPB2 Loss of Function Leads to Disrupted Collagen Trafficking and Juvenile Osteoporosis Phenotypes for gene: COPB2 were set to juvenile osteoporosis Review for gene: COPB2 was set to AMBER Added comment: New gene. One report linking to juvenile osteoporosis Sources: Expert list |
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