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Roosing, S.* ; Rohrschneider, K.* ; Beryozkin, A.* ; Sharon, D.* ; Weisschuh, N.* ; Staller, J.* ; Kohl, S.* ; Zelinger, L.* ; Peters, T.A.* ; Neveling, K.* ; Strom, T.M. ; European Retinal Disease Consortium (*) ; van den Born, L.I.* ; Hoyng, C.B.* ; Klaver, C.C.* ; Roepman, R.* ; Wissinger, B.* ; Banin, E.* ; Cremers, F.P.* ; den Hollander, A.I.*

Mutations in RAB28, encoding a farnesylated small GTPase, are associated with autosomal-recessive cone-rod dystrophy.

Am. J. Hum. Genet. 93, 110-117 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Post-golgi Trafficking ; Retinitis-pigmentosa ; Gene ; Protein ; Rhodopsin ; Photoreceptors ; Transport ; Ortholog ; Rpgrip1l ; Kinase
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Journal American Journal of Human Genetics, The
Quellenangaben Volume: 93, Issue: 1, Pages: 110-117 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)