Bardet Biedl syndrome

Gene: IFT57

Green List (high evidence)

Comment on list classification: As there are 2 unrelated families with ciliopathy reported in literature, together with supportive functional evidence, this gene should now be promoted to Green on Bardet Biedl syndrome.

Created: 9 Apr 2026, 4:06 p.m. | Last Modified: 9 Apr 2026, 4:06 p.m.

Panel Version: 2.14

PMID: 27060890 Thevenon et al., 2016
3 sibs aged 17-25 years, from a consanguineous family, with oral-facial-digital syndrome with skeletal dysplasia and brachymesophalangia. No visual complaints, retinopathy no excluded in the study. All homozygous for IFT57 p.Lys259Lys. It is rare in gnomAD v4., no homozygotes reported. Variant leads to exon skipping, decrease in mRNA stability. Both anterograde ciliary transport and sonic hedgehog signaling were significantly decreased in subjects’ fibroblasts compared to controls.

Created: 9 Apr 2026, 4:04 p.m. | Last Modified: 10 Apr 2026, 9:02 a.m.

Panel Version: 2.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Orofaciodigital syndrome XVIII, OMIM:617927

Publications

• 27060890

I don't know

Comment on list classification: As there is one patient and functional evidence reported, IFT57 should be rated amber with the current evidence.

Created: 4 Jun 2025, 4:49 p.m. | Last Modified: 4 Jun 2025, 4:49 p.m.

Panel Version: 2.7

PMID:40273360 reported a 29-year-old male of Irish descent presenting with rod-cone degeneration leading to legal blindness, post-axial polydactyly, obesity, cognitive impairment, and fatty liver, features suggestive of a clinical diagnosis of Bardet-Biedl Syndrome. He was identified with biallelic variants in IFT57 gene (Val397Glu/Lys225Asnfs*17).

Patient-derived fibroblasts had fewer primary cilia, abnormal ciliary morphology and abnormal anterograde transport in the primary cilia. IFT57 knockout mouse models or RPE cell lines did not form primary cilia. Rescue of IFT57 knockout primary cilia with IFT57-WT restored cilia formation while IFT57-Val397Glu only partially rescued cilia formation in Ift57-KO-mouse cells.

Created: 4 Jun 2025, 4:47 p.m. | Last Modified: 4 Jun 2025, 4:47 p.m.

Panel Version: 2.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Bardet-Biedl syndrome, MONDO:0015229

Publications

• 40273360

I don't know

PMID: 40273360 described one case with Bardet-Biedl syndrome and biallelic variant in IFT57 with some functional evidence.
Sources: Literature

Created: 8 May 2025, 6:15 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Bardet-Biedl syndrome

Publications

• PMID: 40273360