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| Skeletal dysplasia v2.73 | PFN1 | Eleanor Williams Phenotypes for gene: PFN1 were changed from Paget’s disease of bone to Paget’s disease of bone; bone Paget disease MONDO:0005382 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.72 | PFN1 | Eleanor Williams Classified gene: PFN1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.72 | PFN1 | Eleanor Williams Gene: pfn1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.71 | PFN1 | Eleanor Williams edited their review of gene: PFN1: Changed rating: AMBER; Changed phenotypes: bone Paget disease MONDO:0005382; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.71 | PFN1 | Eleanor Williams commented on gene: PFN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.20 | PFN1 |
Zornitza Stark gene: PFN1 was added gene: PFN1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: PFN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PFN1 were set to 32392277; 31991009; 31346562; 32589291; 22801503 Phenotypes for gene: PFN1 were set to Paget’s disease of bone Review for gene: PFN1 was set to AMBER Added comment: A new phenotype association for this gene has been reported: Paget’s disease of bone (PDB). Haploinsuffciency has been linked to PDB in 2 families with the same truncating frameshift variant (unsure if the families are related, both families are from the same region in Italy). Functional studies of this truncating variant showed abnormal protein aggregates (PMID: 32392277, 31991009). An osteoclast-specific conditional null mouse model confirmed the skeletal phenotype (PMID: 31346562). Missense variants in this gene have been previously associated with ALS (PMID: 22801503). Due to these different phenotype associations, it has been suggested that this gene can cause multisystem proteinopathy (PMID: 32589291). Sources: Literature |
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| Skeletal dysplasia v1.176 | FN1 | Eleanor Williams Added comment: Comment on mode of pathogenicity: Only missense or inframe deletions reported to date. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.176 | FN1 | Eleanor Williams Mode of pathogenicity for gene: FN1 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.175 | FN1 | Eleanor Williams Classified gene: FN1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.175 | FN1 | Eleanor Williams Added comment: Comment on list classification: More than 3 cases reported of plausible disease causing mutations found in the FN1 gene in patients with a relevant phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.175 | FN1 | Eleanor Williams Gene: fn1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.174 | FN1 | Eleanor Williams Publications for gene: FN1 were set to 29100092 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.173 | FN1 | Eleanor Williams Mode of inheritance for gene: FN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.172 | FN1 |
Eleanor Williams commented on gene: FN1: This gene is associated with Spondylometaphyseal dysplasia, corner fracture type (#184255) in OMIM. PMID: 29100092 - Lee et al 2017 - 7 cases. Variants in FN1 found in patients from 7 families with Spondylometaphyseal dysplasias with corner fractures. 2 cases were familial, the rest were de novo mutations. In the two familial cases inheritance was autosomal dominant. All FN1 variants discovered in this study are absent from the ExAC Browser and affect highly conserved residues. 6 of the variants were missense, and one was an inframe deletion. PMID: 30599297 - Costantini et al 2019 - 5 cases. Using WGS/WES or targeted Sanger sequencing they identified 5 heterozygous missense variants in FN1 in patients with spondylometaphyseal dysplasia with "corner fractures" (SMD-CF). In two families the variant was inherited from an affected parent. None of the patients had impaired renal function. |
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| Skeletal dysplasia v1.153 | FN1 |
Eleanor Williams Added phenotypes Spondylometaphyseal dysplasia, corner fracture type 184255 for gene: FN1 Publications for gene FN1 were changed from to 29100092 |
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| Skeletal dysplasia v1.147 | FN1 | Tracy Lester reviewed gene: FN1: Rating: GREEN; Mode of pathogenicity: Other - please provide details in the comments; Publications: 29100092; Phenotypes: Spondylometaphyseal dysplasia, corner fracture type 184255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.146 | FN1 | Eleanor Williams reviewed gene: FN1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.145 | FN1 |
Eleanor Williams gene: FN1 was added gene: FN1 was added to Skeletal dysplasia. Sources: NHS GMS Mode of inheritance for gene: FN1 was set to |
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