Skeletal dysplasiaGene: FN1
Spondylometaphyseal dysplasias gp of SD - >3 cases reported. no truncating/fs reported to date.; Review on behalf of Tracy Lester
Created: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spondylometaphyseal dysplasia, corner fracture type 184255
Mode of pathogenicity
Other - please provide details in the comments
Comment on mode of pathogenicity: Only missense or inframe deletions reported to date.
Created: 17 Jul 2019, 11:15 a.m. | Last Modified: 17 Jul 2019, 11:15 a.m.
Panel Version: 1.176
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.
Created: 17 Jul 2019, 11:14 a.m. | Last Modified: 17 Jul 2019, 11:14 a.m.
Panel Version: 1.175
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.
Created: 17 Jul 2019, 11:12 a.m. | Last Modified: 17 Jul 2019, 11:12 a.m.
Panel Version: 1.172
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: FN1; Initial rating suggestion: Green
Created: 6 Mar 2019, 11:36 a.m.
Mode of pathogenicity for gene: FN1 was changed from to Other
Gene: fn1 has been classified as Green List (High Evidence).
Publications for gene: FN1 were set to 29100092
Mode of inheritance for gene: FN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Spondylometaphyseal dysplasia, corner fracture type 184255 for gene: FN1 Publications for gene FN1 were changed from to 29100092
gene: FN1 was added gene: FN1 was added to Skeletal dysplasia. Sources: NHS GMS Mode of inheritance for gene: FN1 was set to