Differences in sex development

Gene: FGFR2

Removed the expert review tag as expert opinion from a member of the Genomics England clinical team was obtained.

Created: 5 Oct 2022, 11:07 p.m. | Last Modified: 5 Oct 2022, 11:07 p.m.

Panel Version: 2.66

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype.

After consulting with the Genomics England Clinical Team, it was decided that this gene should be rated Amber. Helen Brittain (Genomics England):
"In the fetal cases the potential DSD phentoype is very mild and eclipsed by the skeletal / craniosynostosis presentation."

Created: 19 Mar 2021, 12:51 p.m. | Last Modified: 19 Mar 2021, 12:51 p.m.

Panel Version: 2.45

Green List (high evidence)

PMID: 26362256 - 1 individual with craniosynostosis and XY sex reversal and a missense variant. Phenotype recapitulated using mouse model, concludes a LOF mechanism.

PMID: 18155190 - partial null mutant mouse model shows XY sex reversal

PMID: 2238701 - 4 fetuses with de novo mutations and a skeletal disorder 3/4 had clitoromegaly, last fetus only had radiograph available. p.(Met391Arg) is recurring, variants are supported by functional studies showing protein mislocalization

Mutations reported for all other FGFR2-related conditions have a GOF mechanism
Sources: Expert list

Created: 15 Jul 2020, 7:58 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
LADD syndrome 149730; Bent bone dysplasia syndrome 614592

Publications

• 26362256
• 18155190