Skeletal Dysplasia_Fetal

Gene: IFITM5

Green List (high evidence)

Comment on mode of pathogenicity: LoF not established, alternative neomorph/GoF postulated but not yet conclusively proven

Created: 15 Nov 2021, 5:53 a.m. | Last Modified: 15 Nov 2021, 5:53 a.m.

Panel Version: 0.476

- A recurrent c.-14C>T variant has been reported in many patients with type V OI. It introduces an alternative in-frame start codon upstream that is stronger than the reference start codon in transfected HEK cells (PMIDs: 22863190, 22863195). However, the effect of mutant protein (5 amino acids longer) remains unknown but neomorphic mechanism is a widely accepted hypothesis (PMIDs: 25251575, 32383316).

- Missense p.(S40L) variant has a different disease mechanism to that of the recurrent 5'UTR variant: SERPINF1 gene expression and PEDF secretion was increased by the 5'UTR variant but decreased by the p.(S40L) substitution (PMID: 24519609).

Created: 15 Nov 2021, 1:21 a.m. | Last Modified: 15 Nov 2021, 1:21 a.m.

Panel Version: 0.448

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Osteogenesis imperfecta, type V MIM#610967

Publications

• 22863190
• 22863195
• 32383316
• 24519609

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice