Arthrogryposis
Gene: FBN2
The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.Created: 11 Mar 2022, 1:41 p.m. | Last Modified: 11 Mar 2022, 1:41 p.m.
Panel Version: 3.154
It would appear from PMIDs 33571691, 25558065 & 28383543 that biallelic variants should be considered for this gene and as such the MOI should be changed to BOTH monallelic and biallelic, autosomal or pseudoautosomal.Created: 28 Apr 2021, 12:11 p.m. | Last Modified: 28 Apr 2021, 12:11 p.m.
Panel Version: 3.95
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Association between mono-allelic variants and CCA is well established.
Kloth (2021): report biallelic FBN2 variants (PTC/missense) in a teenager with severe CCA, including cardiac defects, mild scoliosis and muscular involvement. Carrier parents both "healthy/unaffected". Phenotype matches mouse K/O.
Authors performed a literature review and identified an additional 2 homozygous patients (both missense variants) with
- fetal akinesia, brain ischemia and neonatal death
- severe muscle weakness with bilateral clubfeet, a pronounced gait disturbance, recurrent patellar dislocations, flexion contractures, camptodactyly, widespread striae and an unusual myofibrillar disorganization, variation in fiber size and atrophic fibers in muscle biopsyCreated: 17 Apr 2021, 7:50 a.m. | Last Modified: 17 Apr 2021, 7:50 a.m.
Panel Version: 3.91
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Contractural arachnodactyly, congenital MIM#121050
Publications
Comment on mode of pathogenicity: Dominant negative mutationsCreated: 4 Jan 2017, 4:17 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Contractural arachnodactyly, congenital 121050
Publications
Mode of pathogenicity
Other
Tag Q2_21_MOI was removed from gene: FBN2.
Source NHS GMS was added to FBN2. Mode of inheritance for gene FBN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FBN2 were set to 7493032; 33571691
Tag Q2_21_MOI tag was added to gene: FBN2.
Phenotypes for gene: FBN2 were changed from Contractural arachnodactyly, congenital 121050 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Publications for gene: FBN2 were set to 7493032
16th Jan 2016: This gene panel was extensively revised with the addition of 101 green genes and review by Alice Gardham. Due to this extensive change to the panel, the decision was made to promote it to the next major version, version 2.
This gene has been classified as Green List (High Evidence).
FBN2 was added to Arthrogryposispanel. Sources: Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
Phenotypes for FBN2 were set to Contractural arachnodactyly, congenital 121050
Publications for FBN2 were set to 7493032
Mode of pathogenicity for FBN2 was changed to Other - please provide details in the comments
This gene has been classified as Green List (High Evidence).
FBN2 was added to Arthrogryposispanel. Sources: Expert list
FBN2 was created by ellenmcdonagh