IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans
Bakey, Z.; Cabrera, O. A.; Hoefele, J.; Antony, D.; Wu, K.; Stuck, M. W.; Micha, D.; Eguether, T.; Smith, A. O.; van der Wel, N.; Strittmatter, L.; Beales, P. L.; Jonassen, J. A.; Thiffault, I.; Cadieux-Dion, M.; Boyes, L.; Sharif, S.; Tuysuz, B.; Dunstheimer, D.; Niessen, H.; Devine, W.; Lo, C. W.; Mitchison, H. M.; Schmidts, M.; Pazour, G. J.
Show abstract
Motile and non-motile cilia are critical to mammalian development and health. Assembly of these organelles depends on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). A series of human and mouse IFT74 variants were studied to understand the function of this IFT subunit. Humans missing exon 2, which codes for the first 40 residues, presented an unusual combination of ciliary chondrodysplasia and mucociliary clearance disorders while individuals carrying biallelic splice site variants developed a lethal skeletal chondrodysplasia. In mice, variants thought to remove all Ift74 function, completely block ciliary assembly and result in midgestational lethality. A mouse allele that removes the first 40 amino acids, analogous to the human exon 2 deletion, results in a motile cilia phenotype with mild skeletal abnormalities. In vitro studies suggest that the first 40 amino acids of IFT74 are dispensable for binding of other IFT subunits but are important for tubulin binding. Higher demands on tubulin transport in motile cilia compared to primary cilia could account for the motile cilia phenotype observed in human and mice.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Mutation of CFAP57 causes primary ciliary dyskinesia by disrupting theasymmetric targeting of a subset of ciliary inner dynein arms 94%
- Tulp3 quantitative alleles titrate requirements for viability, brain development, and kidney homeostasis but do not suppress Zfp423 mutations in mice. 94%
- Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease 93%
Similar papers in this journal
- Biallelic pathogenic variants in TRMT1 disrupt tRNA modification and induce a syndromic neurodevelopmental disorder 95%
- Mutations in MYLPF cause a novel segmental amyoplasia that manifests as distal arthrogryposis 95%
- Missense variants affecting the actin-binding domains of PLS3 cause X-linked congenital diaphragmatic hernia and body wall defects 95%
Similar papers in this journal
- Deficiency of the minor spliceosome component U4atac snRNA secondarily results in ciliary defects 95%
- A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability 95%
- The proteasome regulator PI31 is required for protein homeostasis, synapse maintenance and neuronal survival in mice 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.