Mutations in RAB28, Encoding a Farnesylated Small GTPase, Are Associated with Autosomal-Recessive Cone-Rod Dystrophy
| Autor: | Roosing, S., Rohrschneider, K., Beryozkin, A., Sharon, D., Weisschuh, N., Staller, J., Kohl, S., Zelinger, L., Peters, T.A., Neveling, K., Strom, T.M., Disease, C. European Retina, Born, L.I. van den, Hoyng, C.B., Klaver, C.C., Roepman, R., Wissinger, B., Banin, E., Cremers, F.P.M., Hollander, A.I. den |
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| Přispěvatelé: | Ophthalmology |
| Rok vydání: | 2013 |
| Předmět: |
Genetics and epigenetic pathways of disease [NCMLS 6]
genetic structures Visual Acuity GTPase Retinal Pigment Epithelium Retinal Rod Photoreceptor Cells Evaluation of complex medical interventions Genomic disorders and inherited multi-system disorders [NCEBP 2] Genetics(clinical) Child Genetics (clinical) Genetics 0303 health sciences 030305 genetics & heredity Homozygote Chromosome Mapping Disease gene identification Pedigree Isoenzymes Protein Transport medicine.anatomical_structure Codon Nonsense Retinitis Pigmentosa Adult Adolescent Nonsense mutation Protein Prenylation Genes Recessive Biology Retina Genomic disorders and inherited multi-system disorders [IGMD 3] 03 medical and health sciences Report Retinitis pigmentosa Ciliary rootlet medicine Animals Humans Genetic Predisposition to Disease Cilia Photoreceptor Connecting Cilium Genetic Association Studies 030304 developmental biology Retinal pigment epithelium Genetics and epigenetic pathways of disease Plasticity and memory [NCMLS 6] medicine.disease Molecular biology eye diseases Rats Alternative Splicing Gene Expression Regulation rab GTP-Binding Proteins Protein prenylation Rab sense organs Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6] |
| Zdroj: | American Journal of Human Genetics, 93, 110-7 The American Journal of Human Genetics; Vol 93 American Journal of Human Genetics, 93, 1, pp. 110-7 American Journal of Human Genetics, 93(1), 110-117. Cell Press |
| ISSN: | 0002-9297 |
| Popis: | Item does not contain fulltext The majority of the genetic causes of autosomal-recessive (ar) cone-rod dystrophy (CRD) are currently unknown. A combined approach of homozygosity mapping and exome sequencing revealed a homozygous nonsense mutation (c.565C>T [p.Glu189*]) in RAB28 in a German family with three siblings with arCRD. Another homozygous nonsense mutation (c.409C>T [p.Arg137*]) was identified in a family of Moroccan Jewish descent with two siblings affected by arCRD. All five affected individuals presented with hyperpigmentation in the macula, progressive loss of the visual acuity, atrophy of the retinal pigment epithelium, and severely reduced cone and rod responses on the electroretinogram. RAB28 encodes a member of the Rab subfamily of the RAS-related small GTPases. Alternative RNA splicing yields three predicted protein isoforms with alternative C-termini, which are all truncated by the nonsense mutations identified in the arCRD families in this report. Opposed to other Rab GTPases that are generally geranylgeranylated, RAB28 is predicted to be farnesylated. Staining of rat retina showed localization of RAB28 to the basal body and the ciliary rootlet of the photoreceptors. Analogous to the function of other RAB family members, RAB28 might be involved in ciliary transport in photoreceptor cells. This study reveals a crucial role for RAB28 in photoreceptor function and suggests that mutations in other Rab proteins may also be associated with retinal dystrophies. |
| Databáze: | OpenAIRE |
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