Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: FGFR3
Green (specific GOF variants in ex7 & 10 only: e.g. P250R, A391E) - Exons 7 and 10 are prescreened in R99. Other GOF variants are associated with other, mainly skeletal, disorders. Truncating/fs variants have not been reported in skeletal phenotypes. ; Review on behalf of Tracy Lester/Andrew WilkieCreated: 5 Mar 2019, 11:33 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Muenke syndrome; Crouzon syndrome with acanthosis nigricans
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
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: FGFR3; Suggested initial gene rating: greenCreated: 5 Mar 2019, 11:21 a.m.
Comment on list classification: Current diagnosticsCreated: 1 Feb 2016, 11:07 a.m.
Only p.Pro250Arg and p.Ala391Glu mutations classically associated with craniosynostosis; other gain-of-function mutations in FGFR3 cause skeletal dysplasias (some which may also manifest craniosynostosis)Created: 14 Sep 2015, 11:47 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Muenke syndrome; Crouzon syndrome with acanthosis nigricans
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Source NHS GMS was added to FGFR3. Rating Changed from Green List (high evidence) to Green List (high evidence)
Phenotypes for FGFR3 were set to Muenke syndrome; Crouzon syndrome with acanthosis nigricans
Publications for FGFR3 were set to 9042914; 7493034
Mode of pathogenicity for FGFR3 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for FGFR3 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
FGFR3 was added to Craniosynostosis syndromespanel. Sources: Eligibility statement prior genetic testing
FGFR3 was added to Craniosynostosis syndromespanel. Sources: Expert list