Mutations in AGBL5, Encoding alpha-Tubulin Deglutamylase, Are Associated With Autosomal Recessive Retinitis Pigmentosa
| Autor: | Sultana M.H. Faradz, Galuh D.N. Astuti, Gavin Arno, F L Raymond, K. Carss, L. I. van den Born, Hanka Venselaar, Laurence H M Pierrache, Frans P.M. Cremers, Rob W.J. Collin, A. R. Webster, Sarah Hull |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Candidate gene Adolescent DNA Mutational Analysis Genes Recessive Carboxypeptidases Biology Compound heterozygosity Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Young Adult 03 medical and health sciences symbols.namesake Tubulin Retinitis pigmentosa medicine Humans Missense mutation Exome Allele Sensory disorders Radboud Institute for Molecular Life Sciences [Radboudumc 12] Child Gene Alleles Exome sequencing Sanger sequencing Genetics Homozygote DNA Middle Aged medicine.disease Molecular biology eye diseases Pedigree Phenotype 030104 developmental biology Child Preschool Mutation symbols Female Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] Retinitis Pigmentosa |
| Zdroj: | Investigative Ophthalmology and Visual Science, 57, 6180-6187 Investigative Ophthalmology and Visual Science, 57, 14, pp. 6180-6187 |
| ISSN: | 0146-0404 |
| Popis: | Contains fulltext : 167966.pdf (Publisher’s version ) (Open Access) Purpose: AGBL5, encoding ATP/GTP binding protein-like 5, was previously proposed as an autosomal recessive retinitis pigmentosa (arRP) candidate gene based on the identification of missense variants in two families. In this study, we performed next-generation sequencing to reveal additional RP cases with AGBL5 variants, including protein-truncating variants. Methods: Whole-genome sequencing (WGS) or whole-exome sequencing (WES) was performed in three probands. Subsequent Sanger sequencing and segregation analysis were performed in the selected candidate genes. The medical history of individuals carrying AGBL5 variants was reviewed and additional ophthalmic examinations were performed, including fundus photography, fundus autofluorescence imaging, and optical coherence tomography. Results: AGBL5 variants were identified in three unrelated arRP families, comprising homozygous variants in family 1 (c.1775G>A:p.(Trp592*)) and family 2 (complex allele: c.[323C>G; 2659T>C]; p.[(Pro108Arg; *887Argext*1)]), and compound heterozygous variants (c.752T>G:p.(Val251Gly) and c.1504dupG:p.(Ala502Glyfs*15)) in family 3. All affected individuals displayed typical RP phenotypes. Conclusions: Our study convincingly shows that variants in AGBL5 are associated with arRP. The identification of AGBL5 and TTLL5, a previously described RP-associated gene encoding the tubulin tyrosine ligase-like family, member 5 protein, highlights the importance of poly- and deglutamylation in retinal homeostasis. Further studies are required to investigate the underlying disease mechanism associated with AGBL5 variants. |
| Databáze: | OpenAIRE |
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