TTLL5 gene

Overview

Gene (OMIM No.)	TTLL5 (#612268)
Function of gene/protein	Protein: tubulin tyrosine ligase-like family, member 5 Polyglutamylation of the primary cilia Normal functioning of sperm flagella Stabilising the microtubules of the photoreceptor cilia
Clinical phenotype (OMIM phenotype no.)	Cone-rod dystrophy 19 (#615860)
Inheritance	Autosomal recessive
Ocular features	Consistent fundal phenotype best appreciated on fundus autofluorescence (FAF) imaging Hyper-autofluorescent perifoveal ring surrounding an area of irregular foveal autofluorescence Outer retinal and RPE degeneration mainly confined to the foveal region observed on OCT Normal AF signal peripheral to the perifoveal ring
Visual function	Patients usually present during 30s to 40s with central visual disturbance but earlier onset disease (childhood) have been reported in minority Progressive central vision deterioration and mild peripheral visual field constriction
Systemic features	Infertility due to significant reduction in sperm motility reported in two unrelated male patients harbouring two truncating TTLL5 variants Not a consistent finding as other affected males with two truncating alleles have children
Key investigations	Electrophysiology Fundus autofluorescence (FAF) Optical coherence tomography (OCT) Kinetic perimetry
Molecular diagnosis	Next generation sequencing Targeted gene panels (retinal) Whole exome sequencing Whole genome sequencing
Management	Ocular Management of cone-rod dystrophy
Therapies under research	None at present
Further information	Medline Plus

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References

Backer CB, Gutzman JH, Pearson CG, Cheeseman IM. CSAP localizes to polyglutamylated microtubules and promotes proper cilia function and zebrafish development. Mol Biol Cell. 2012;23(11):2122-2130
Lee GS, He Y, Dougherty EJ, et al. Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility. J Biol Chem. 2013;288(21):15167-15180
Sergouniotis PI, Chakarova C, Murphy C, et al. Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy. Am J Hum Genet. 2014;94(5):760-769
Bedoni N, Haer-Wigman L, Vaclavik V, et al. Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility. Hum Mol Genet. 2016;25(20):4546-4555

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Updated on January 24, 2021

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