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Skeletal dysplasia v9.33 FBN2 Ida Ertmanska changed review comment from: Comment on list classification: Heterozygous variants in FBN2 are known to cause congenital contractural arachnodactyly. These patients do not tend to have skeletal defects beyond mild digit anomalies (camptodactyly, arachnodactyly). Tall stature was found to be associated with FBN1, but I did not find evidence of association with FBN2 variants. Hence, this gene should be downgraded to Red on the Skeletal dysplasia panel. An expert-review tag was added as this is a proposed demotion from Green rating.; to: Comment on list classification: Heterozygous variants in FBN2 are known to cause congenital contractural arachnodactyly. These patients do not tend to have skeletal defects beyond mild digit anomalies (camptodactyly, arachnodactyly). Tall stature was found to be associated with FBN1, but I did not find evidence of association with FBN2 variants. There are also 4 cases reported with biallelic FBN2 variants and various presentations, none with skeletal manifestations beyond digit anomalies. Hence, this gene should be downgraded to Red on the Skeletal dysplasia panel. An expert-review tag was added as this is a proposed demotion from Green rating.
Skeletal dysplasia v9.33 FBN2 Ida Ertmanska edited their review of gene: FBN2: Changed rating: RED
Skeletal dysplasia v9.33 FBN2 Ida Ertmanska Deleted their comment
Skeletal dysplasia v9.33 FBN2 Ida Ertmanska commented on gene: FBN2: Comment on list classification: Heterozygous variants in FBN2 are known to cause congenital contractural arachnodactyly. These patients do not tend to have skeletal defects beyond mild digit anomalies (camptodactyly, arachnodactyly). Tall stature was found to be associated with FBN1, but I did not find evidence of association with FBN2 variants. Hence, this gene should be downgraded to Red on the Skeletal dysplasia panel. An expert-review tag was added as this is a proposed demotion from Green rating.
Skeletal dysplasia v9.33 FBN2 Ida Ertmanska commented on gene: FBN2: Comment on list classification: Heterozygous variants in FBN2 are known to cause congenital contractural arachnodactyly. These patients do not tend to have skeletal defects beyond mild digit anomalies (camptodactyly, arachnodactyly). Tall stature was found to be associated with FBN1, but I did not find evidence of association with FBN2 variants. Hence, this gene should be downgraded to Red on the Skeletal dysplasia panel. An expert-review tag was added as this is a proposed demotion from Green rating.
Skeletal dysplasia v9.33 FBN2 Ida Ertmanska Tag Q3_26_expert_review tag was added to gene: FBN2.
Skeletal dysplasia v9.33 FBN2 Ida Ertmanska Tag Q3_26_demote_red tag was added to gene: FBN2.
Skeletal dysplasia v9.33 FBN2 Ida Ertmanska edited their review of gene: FBN2: Added comment: MONOALLELIC CASES:
PMID: 35360850 Sun et al., 2022
Report of 27 congenital contractural arachnodactyly (CCA) patients from 10 families, harbouring heterozygous FBN2 variants (mostly missense, 2 confirmed de novo).
Arachnodactyly (27/27, 100%), crumpled ears (26/27, 96.3%), camptodactyly (26/27, 96.3%), and muscle hypoplasia (22/26, 85%) were observed in almost all recruited cases. More than half patients (16/25, 64%) presented with contracture of large joints, including elbow, wrist, knee, ankle, and shoulder. 54% patients (13/24) present with kyphosis or scoliosis; 29% patients (7/24) presented with pectus deformity, including four patients with pectus carinatum and three patients with pectus excavatum; 74% patients (17/23) presented with high arched palate and 71% patients (17/24) presented with micrognathia; 33% patients (9/27) presented with pes planus.
No wider skeletal defects noted beyond mild digit anomalies. No patient presented with dolichostenomelia (disproportionately long limbs).

PMID: 24833718 Buchan et al., 2014
Study of 852 adolescent idiopathic scoliosis cases and 669 controls.
In individuals of European ancestry, rare variants in FBN1 and FBN2 were enriched in severely affected AIS cases (7.6%) compared with in-house controls (2.4%) (OR = 3.5, P = 5.46 × 10(-4)) and Exome Sequencing Project controls (2.3%) (OR = 3.5, P = 1.48 × 10(-6))
FBN1 variants associated with tall stature - not noted in FBN2.; Changed publications to: 24833718, 25558065, 28383543, 33571691, 35360850, 38791509
Skeletal dysplasia v9.33 FBN2 Ida Ertmanska reviewed gene: FBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25558065, 28383543, 33571691, 38791509; Phenotypes: Contractural arachnodactyly, congenital, OMIM:121050, congenital contractural arachnodactyly, MONDO:0007363; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v2.184 FBN2 Eleanor Williams Tag Q2_21_MOI was removed from gene: FBN2.
Skeletal dysplasia v2.184 FBN2 Eleanor Williams commented on gene: FBN2: The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Skeletal dysplasia v2.183 FBN2 Eleanor Williams Mode of inheritance for gene FBN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.91 FBN2 Sarah Leigh Deleted their comment
Skeletal dysplasia v2.91 FBN2 Sarah Leigh commented on gene: FBN2: 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.
Skeletal dysplasia v2.91 FBN2 Sarah Leigh edited their review of gene: FBN2: Added comment: 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.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v2.91 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Skeletal dysplasia v2.90 FBN2 Sarah Leigh Phenotypes for gene: FBN2 were changed from Contractural arachnodactyly, congenital 121050 to Contractural arachnodactyly, congenital OMIM:121050; congenital contractural arachnodactyly MONDO:0007363
Skeletal dysplasia v2.89 FBN2 Sarah Leigh Publications for gene: FBN2 were set to 7493032; 33571691; 25558065; 28383543
Skeletal dysplasia v2.88 FBN2 Sarah Leigh Publications for gene: FBN2 were set to
Skeletal dysplasia v2.87 FBN2 Sarah Leigh Tag Q2_21_MOI tag was added to gene: FBN2.
Skeletal dysplasia v1.153 FBN2 Eleanor Williams Added phenotypes Contractural arachnodactyly, congenital 121050 for gene: FBN2
Skeletal dysplasia v1.147 FBN2 Tracy Lester reviewed gene: FBN2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Contractural arachnodactyly, congenital 121050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v1.146 FBN2 Eleanor Williams reviewed gene: FBN2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v1.145 FBN2 Eleanor Williams Source NHS GMS was added to FBN2.
Rating Changed from Green List (high evidence) to Green List (high evidence)