Rare multisystem ciliopathy disorders

Gene: FAM149B1

I don't know

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: 26 Sep 2019, 1:15 p.m. | Last Modified: 26 Sep 2019, 1:15 p.m.

Panel Version: 1.121

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: 26 Sep 2019, 1:05 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Publications

• 30905400