Neurological ciliopathiesGene: FAM149B1
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, 8:39 a.m. | Last Modified: 2 Oct 2019, 8:39 a.m.
Panel Version: 0.7
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.
Created: 2 Oct 2019, 8:38 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Joubert syndrome; oral-facial-digital syndrome; OFD VI
Gene: fam149b1 has been classified as Amber List (Moderate Evidence).
gene: FAM149B1 was added gene: FAM149B1 was added to Neurological ciliopathies. Sources: Literature Mode of inheritance for gene: FAM149B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM149B1 were set to 30905400 Phenotypes for gene: FAM149B1 were set to Joubert syndrome; oral-facial-digital syndrome; OFD VI Review for gene: FAM149B1 was set to AMBER