Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

A Missense Mutation in RAB28 in a Family with Cone-Rod Dystrophy and Postaxial Polydactyly Prevents Localization of RAB28 to the Primary Cilium

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Retinal Structure in RPE65-Associated Retinal Dystrophy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Five-Year Change in Choroidal Thickness in Relation to Body Development and Axial Eye Elongation: The CCC2000 Eye Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Small Hard Macular Drusen and Associations in 11- to 12-Year-Old Children in the Copenhagen Child Cohort 2000 Eye Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Dual Properties of Lactate in Müller Cells: The Effect of GPR81 Activation

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Crosstalk of Hedgehog and mTORC1 Pathways

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A)

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Description of a family with X-linked oculo-auriculo-vertebral spectrum associated with polyalanine tract expansion in ZIC3

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Purpose: Cone-rod dystrophy (CRD) is a rare hereditary eye disorder that causes progressive degeneration of cone and rod photoreceptors. More than 30 genes, including RAB28, have been associated with CRD; however, only a few RAB28 variants have been reported to be associated with CRD. In this study, we describe two brothers with CRD and a homozygous missense variant, c.55G>A (p.Gly19Arg), in RAB28.

Methods: The missense variant was identified as part of a study investigating underlying genetic defects in a large patient cohort (n = 667) using targeted next-generation sequencing of 125 genes associated with retinal dystrophy. Cellular localization of RAB28 and ciliogenesis in patient fibroblasts were investigated by immunofluorescence microscopy. The effect of the missense variant on RAB28 expression level was investigated by quantitative real-time PCR.

Results: Two brothers of a consanguineous couple presented with CRD, postaxial polydactyly (PAP), and myopia. Both brothers had a homozygous missense RAB28 variant located in the G1 box of the guanosine triphosphate/guanosine diphosphate binding domain of RAB28. This missense variant caused a considerable reduction of RAB28 localized to the cilia, whereas ciliogenesis seemed unaffected.

Conclusions: The missense variant in RAB28 is classified as likely pathogenic with functional effect on protein localization. The combination of retinal dystrophy and PAP are well known from ciliopathies; however, more data are needed to finally conclude that the RAB28 variant described here is the cause of PAP in these brothers.

OriginalsprogEngelsk
Artikelnummer2761939
TidsskriftInvestigative ophthalmology & visual science
Vol/bind61
Udgave nummer2
Sider (fra-til)29
ISSN0146-0404
DOI
StatusUdgivet - 7 feb. 2020

ID: 59747848