Ophthalmological ciliopathies

Gene: FAM149B1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 3:58 p.m. | Last Modified: 24 Feb 2025, 3:58 p.m.

Panel Version: 4.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (five unrelated families and two different variants) for promoting this gene to green rating in the next GMS update.

Created: 19 Jul 2024, 9:21 a.m. | Last Modified: 19 Jul 2024, 9:21 a.m.

Panel Version: 4.4

PMID:34828254 reported the identification of homozygous FAM149B1 variant (c.354_357delinsCACTC/ p.Gln118Hisfs*20) in three adult siblings from a large consanguineous family from Saudi Arabia. This variant is similar to one of the two variants that were previously reported in three unrelated families from Saudi Arabia (c.356_357del/ p.Lys119Ilefs∗18).

This gene has been associated with relevant phenotypes in OMIM (MIM #618763) and Gene2Phenotype (with 'strong' rating on the DD panel).

Created: 19 Jul 2024, 9:19 a.m. | Last Modified: 19 Jul 2024, 9:19 a.m.

Panel Version: 4.1

The OMIM entry for this gene is OMIM:618413, which has been cross-checked with Ensembl, HGNC and G2P. Hence, gene-checked tag has been added.

Created: 17 Oct 2023, 9:47 a.m. | Last Modified: 17 Oct 2023, 9:47 a.m.

Panel Version: 3.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 36, OMIM:618763

Publications

• 34828254

I don't know

Comment on list classification: Comment on list classification: 3 founder variant cases reported plus one other. Some functional data. Changing rating from red to amber based on the 2 independent cases reported.

Created: 2 Oct 2019, 8:36 a.m. | Last Modified: 2 Oct 2019, 8:36 a.m.

Panel Version: 0.11

PMID: 30905400 - Shaheen et al 2019 - report 4 cases in which homozygous variants in the FAM149B1 gene are found in patients with a ciliopathy phenotype that most closely matches Joubert syndrome or Joubert syndrome/oral-facial-digital syndrome (OFD VI) . 3 of the cases in Consanguinity families of Arab origin have the same c.356_357del (p.Lys119Ilefs∗18) variant and haplotype analysis suggests a founder mutation. The fourth case in a Turkish family with Joubert syndrome was found to have a different homozygous truncating variant in the same gene (c.439C>T [p.Gln147∗])). Both variants are predicted to result in truncated proteins.
Functional studies - FAM149B1 encodes a protein of unknown function and mutant fibroblasts were found to have normal ciliogenesis potential. But some cilia-related abnormalities were observed in these cells: abnormal accumulation IFT complex at the distal tips of the cilia, which assumed bulbous appearance, increased length of the primary cilium, and dysregulated SHH signaling.
Sources: Literature

Created: 2 Oct 2019, 8:35 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome; oral-facial-digital syndrome; OFD VI

Publications

• 30905400