ArticleAmerican journal of human genetics2014
Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy-Beyond Classical Gene Candidates.Frontiers in genetics · 2022Pooled it
- Missense variants in KATNA1 alter microtubule dynamics and underlie dominant macular dystrophy.Research square · 2026Article
- Insights into retinal disease and non-tubulin glutamylation from a RPGR-TTLL5 complex structure.The Journal of cell biology · 2026Article
- Genetic and Phenotypic Characterization of a Large Cohort of Patients with BBS1-Retinopathy.Ophthalmology science · 2026Article
- Ciliary Defects in Inherited Retinal Diseases.Advanced genetics (Hoboken, N.J.) · 2026Review
- Rescue of ciliogenesis and hyperglutamylation mutant phenotype in AGBL5BMC molecular and cell biology · 2025Article
- Tapetal-like sheen as a key phenotypical feature inAmerican journal of ophthalmology case reports · 2025Article
- Novel splice variants implicated in inherited retinal dystrophies in two Moroccan families.Molecular biology reports · 2025Article
- Article
- HaploSweep: Detecting and Distinguishing Recent Soft and Hard Selective Sweeps through Haplotype Structure.Molecular biology and evolution · 2024Article
- IQCB1 (NPHP5)-Retinopathy: Clinical and Genetic Characterization and Natural History.American journal of ophthalmology · 2024Article
- Excessive tubulin glutamylation leads to progressive cone-rod dystrophy and loss of outer segment integrity.Human molecular genetics · 2024Article
- RPGR: Deep Phenotyping and Genetic Characterization With Findings Specific to the 3'-end of ORF15.Investigative ophthalmology & visual science · 2023Article
- Systematic assessment of the contribution of structural variants to inherited retinal diseases.Human molecular genetics · 2023Article
- Glutamylation is a negative regulator of microtubule growth.Molecular biology of the cell · 2023Article
- Novel pathogenic variants in Tubulin Tyrosine Like 5 (Molecular vision · 2023Article
- Four different gene-related cone-rod dystrophy: clinical and genetic findings in six Chinese families with diverse modes of inheritance.Frontiers in genetics · 2023Article
- Impaired glutamylation of RPGRProceedings of the National Academy of Sciences of the United States of America · 2022Article
- TTLL1 and TTLL4 polyglutamylases are required for the neurodegenerative phenotypes in pcd mice.PLoS genetics · 2022Article
- Expanding the phenotype of TTLL5-associated retinal dystrophy: a case series.Orphanet journal of rare diseases · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
In a subset of inherited retinal degenerations (including cone, cone-rod, and macular dystrophies), cone photoreceptors are more severely affected than rods; ABCA4 mutations are the most common cause of this heterogeneous class of disorders. To identify retinal-disease-associated genes, we performed exome sequencing in 28 individuals with "cone-first" retinal disease and clinical features atypical for ABCA4 retinopathy. We then conducted a gene-based case-control association study with an internal exome data set as the control group. TTLL5, encoding a tubulin glutamylase, was highlighted as the most likely disease-associated gene; 2 of 28 affected subjects harbored presumed loss-of-function variants: c.[1586_1589delAGAG];[1586_1589delAGAG], p.[Glu529Valfs(∗)2];[Glu529Valfs(∗)2], and c.[401delT(;)3354G>A], p.[Leu134Argfs(∗)45(;)Trp1118(∗)]. We then inspected previously collected exome sequence data from individuals with related phenotypes and found two siblings with homozygous nonsense variant c.1627G>T (p.Glu543(∗)) in TTLL5. Subsequently, we tested a panel of 55 probands with retinal dystrophy for TTLL5 mutations; one proband had a homozygous missense change (c.1627G>A [p.Glu543Lys]). The retinal phenotype was highly similar in three of four families; the sibling pair had a more severe, early-onset disease. In human and murine retinae, TTLL5 localized to the centrioles at the base of the connecting cilium. TTLL5 has been previously reported to be essential for the correct function of sperm flagella in mice and play a role in polyglutamylation of primary cilia in vitro. Notably, genes involved in the polyglutamylation and deglutamylation of tubulin have been associated with photoreceptor degeneration in mice. The electrophysiological and fundus autofluorescence imaging presented here should facilitate the molecular diagnosis in further families.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.