Hand and foot malformations
Gene: FGF9
Association with multiple synostoses syndrome 3:
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.
Association with craniosynostosis: single family and animal model.Created: 1 Feb 2021, 7:34 a.m. | Last Modified: 1 Feb 2021, 7:34 a.m.
Panel Version: 0.6174
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Multiple synostoses syndrome 3, OMIM # 612961; Craniosynostosis
Publications
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.Created: 31 Jan 2021, 11:59 p.m. | Last Modified: 31 Jan 2021, 11:59 p.m.
Panel Version: 0.78
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: 31 Jan 2021, 11:54 p.m. | Last Modified: 31 Jan 2021, 11:54 p.m.
Panel Version: 0.77
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
gene: FGF9 was added gene: FGF9 was added to Hand and foot malformation. Sources: Expert Review Green,Expert list Mode of inheritance for gene: FGF9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: FGF9 were set to Multiple synostoses syndrome type 3 612961