Skeletal dysplasia
Gene: FGF9
Thuresson et al. (2021) identified a de novo heterozygous missense variant in FGF9 (Pro189Arg) in 16‐year old boy with multiple synostoses syndrome. Functional studies showed this variant impairs FGF9 homodimerization, but not FGFR3c binding.
Wu et al. (2009) identified a heterozygous missense variant in FGF9 (S99N) in 5-generation Chinese family with AD multiple synostoses syndrome. Variant segregated with disease and was not found in 250 unrelated ethnically matched controls. Biochemical analysis reveals that S99N mutation in FGF9 leads to significantly impaired FGF signaling, as evidenced by diminished activity of Erk1/2 pathway and decreased beta-catenin and c-Myc expression when compared with wild-type FGF9.
Rodriguez-Zabala et al. (2017) identified a heterozygous missense variant in FGF9 (R62G) in a Spanish father and son with multiple synostoses syndrome and craniosynostosis. Variant segregated with disease in the family and was not found in 150 Spanish controls or in the gnomAD database. The mutation appeared to have arisen de novo in the father, as it was not detected in the biologically confirmed unaffected paternal grandparents. Modeling based upon the crystal structure and functional studies confirmed its pathogenicity showing that it impaired homodimerization and FGFR3 binding.
Sentchordi-Montané et al. (2021) identified a heterozygous missense variant in FGF9 (Asn143Tyr) in a young girl with a multiple joint synostosis.Created: 1 Feb 2021, 9:13 a.m. | Last Modified: 1 Feb 2021, 9:13 a.m.
Panel Version: 2.80
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Multiple synostoses syndrome 3, OMIM # 612961
Publications
Variants in this GENE are reported as part of current diagnostic practice
Defects in joint formation and synostoses gp of SD. Two cases reported, one with multiple synostoses syndrome and one with sagittal suture synostosis. Missense variants with no functional studies. (Wu et al 2009, Rodriguez-Zabala et al 2017). Dominant mouse mutant has elbow knee synostosis - ? Amber; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Multiple synostoses syndrome type 3 612961
Publications
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 11:08 a.m. | Last Modified: 11 Oct 2023, 11:08 a.m.
Panel Version: 4.20
Comment on list classification: Promoting this gene from red to amber but with a recommendation for GREEN rating following GMS review as 4 unrelated cases with variants in FGF9 and a phenotype of multiple synostoses syndrome.Created: 30 May 2023, 12:26 a.m. | Last Modified: 30 May 2023, 12:26 a.m.
Panel Version: 4.8
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: FGF9; Initial rating suggestion: amberCreated: 6 Mar 2019, 11:36 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Comment on mode of inheritance: from publication PMID 19589401Created: 10 Apr 2017, 12:56 p.m.
Single variant c.296G>A p.(Ser99 Asn) reported in 12 affected members of a 5-generation Chinese family with autosomal dominant multiple synostoses syndrome. Supporting functional data provided.
Probable G2P associationCreated: 10 Apr 2017, 12:52 p.m.
Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve AbbsCreated: 27 Jul 2016, 9:35 a.m.
Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)Created: 21 Jun 2016, 12:48 p.m.
Publications
Tier 2Created: 17 Jun 2016, 8:04 a.m.
Mode of inheritance
Unknown
Phenotypes
Multiple synostoses syndrome 3 612961
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_23_promote_green was removed from gene: FGF9.
Source Expert Review Green was added to FGF9. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: FGF9 were changed from ?Multiple synostoses syndrome type 3 612961 to Multiple synostoses syndrome 3, OMIM:612961; multiple synostoses syndrome 3, MONDO:0013064
Publications for gene: FGF9 were set to 19589401
Gene: fgf9 has been classified as Amber List (Moderate Evidence).
Tag watchlist was removed from gene: FGF9. Tag Q2_23_promote_green tag was added to gene: FGF9.
Added phenotypes ?Multiple synostoses syndrome type 3 612961 for gene: FGF9
Source NHS GMS was added to FGF9.
Mode of inheritance for FGF9 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for FGF9 were set to 19589401
This gene has been classified as Red List (Low Evidence).
Phenotypes for FGF9 were set to ?Multiple synostoses syndrome type 3 612961
Promoted to version 1 9th August 2016
Phenotypes for FGF9 were set to Multiple synostoses syndrome type 3 612961
Mode of inheritance for FGF9 was changed to Unknown
This gene has been classified as Green List (High Evidence).
FGF9 was created by sleigh
FGF9 was added to Unexplained skeletal dysplasiapanel. Sources: