C21orf2 is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium

Publication type:
Journal article
Metadata:
Autoren
  • Arif O Khan
  • Tobias Eisenberger
  • Kerstin Nagel-Wolfrum
  • Uwe Wolfrum
  • Hanno J Bolz
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000365285100027&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1136/bjophthalmol-2015-307277
eISSN
1468-2079
Externe Identifier
  • Clarivate Analytics Document Solution ID: CW8YJ
  • PubMed Identifier: 26294103
ISSN
0007-1161
Ausgabe der Veröffentlichung
12
Zeitschrift
BRITISH JOURNAL OF OPHTHALMOLOGY
Paginierung
1725 - 1731
Datum der Veröffentlichung
2015
Status
Published
Titel
<i>C21orf2</i> is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium
Sub types
  • Article
Ausgabe der Zeitschrift
99

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Arif O Khan
  • Tobias Eisenberger
  • Kerstin Nagel-Wolfrum
  • Uwe Wolfrum
  • Hanno J Bolz
DOI
10.1136/bjophthalmol-2015-307277
eISSN
1468-2079
ISSN
0007-1161
Ausgabe der Veröffentlichung
12
Zeitschrift
British Journal of Ophthalmology
Sprache
en
Online publication date
2015
Paginierung
1725 - 1731
Datum der Veröffentlichung
2015
Status
Published
Herausgeber
BMJ
Herausgeber URL
http://dx.doi.org/10.1136/bjophthalmol-2015-307277
Datum der Datenerfassung
2020
Titel
<i>C21orf2</i>is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium
Ausgabe der Zeitschrift
99

Data source: Crossref

Abstract
<h4>Background/aim</h4>We have noted a phenotype of early-onset retinal dystrophy with macular staphyloma but without high myopia. The aim of this study is to report the underlying genetic mutations and the subcellular localisation of the gene product in the retina.<h4>Methods</h4>Retrospective case series (2012-2015); immunohistochemical analyses of mammalian retina for in situ protein localisation.<h4>Results</h4>All three probands were first noted to have decreased vision at 3-6 years old which worsened over time. At ages 39, 37 and 12 years old, all had similar retinal findings: dystrophic changes (retinal pigment epithelium mottling, vessel narrowing), macular staphyloma (despite only mild myopia or high hyperopia), and non-recordable electroretinography. All harboured homozygous mutations in C21orf2, a gene recently suggested to be associated with retinal dystrophy but of unknown function. Two had a frameshift deletion c.436_466del (p.Glu146Serfs*6). The third had a missense mutation affecting a highly conserved residue (p.Cys61Tyr) and was short (below the 3rd percentile) and obese (50th percentile for weight despite short stature). Immunohistochemical studies in human, pig and mouse retinas localised C21orf2 protein to the ciliary structures of the photoreceptor cell (the daughter basal body, the centriole adjacent to the basal body, and the connecting cilium).<h4>Conclusions</h4>This retinal dystrophy phenotype is caused by recessive mutations in C21orf2 and can be considered a retinal ciliopathy as C21orf2 encodes a protein that localises to photoreceptor ciliary structures. The short stature and obesity noted in the youngest girl suggest that for some patients biallelic C21orf2 mutations may result in syndromic ciliopathy.
Addresses
  • Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Autoren
  • Arif O Khan
  • Tobias Eisenberger
  • Kerstin Nagel-Wolfrum
  • Uwe Wolfrum
  • Hanno J Bolz
DOI
10.1136/bjophthalmol-2015-307277
eISSN
1468-2079
Externe Identifier
  • PubMed Identifier: 26294103
Open access
false
ISSN
0007-1161
Ausgabe der Veröffentlichung
12
Zeitschrift
The British journal of ophthalmology
Schlüsselwörter
  • Retina
  • Animals
  • Sus scrofa
  • Humans
  • Mice
  • Dilatation, Pathologic
  • Proteins
  • Cytoskeletal Proteins
  • Magnetic Resonance Imaging
  • Tomography, Optical Coherence
  • Electroretinography
  • Blotting, Western
  • Retrospective Studies
  • Polymerase Chain Reaction
  • Pedigree
  • Consanguinity
  • Amino Acid Sequence
  • Genes, Recessive
  • Frameshift Mutation
  • Mutation, Missense
  • Molecular Sequence Data
  • Adult
  • Child
  • Tissue Donors
  • Female
  • Photoreceptor Connecting Cilium
  • Retinal Dystrophies
Sprache
eng
Medium
Print-Electronic
Online publication date
2015
Paginierung
1725 - 1731
Datum der Veröffentlichung
2015
Status
Published
Datum der Datenerfassung
2015
Titel
C21orf2 is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Case Reports
Ausgabe der Zeitschrift
99

Data source: Europe PubMed Central

Abstract
BACKGROUND/AIM: We have noted a phenotype of early-onset retinal dystrophy with macular staphyloma but without high myopia. The aim of this study is to report the underlying genetic mutations and the subcellular localisation of the gene product in the retina. METHODS: Retrospective case series (2012-2015); immunohistochemical analyses of mammalian retina for in situ protein localisation. RESULTS: All three probands were first noted to have decreased vision at 3-6 years old which worsened over time. At ages 39, 37 and 12 years old, all had similar retinal findings: dystrophic changes (retinal pigment epithelium mottling, vessel narrowing), macular staphyloma (despite only mild myopia or high hyperopia), and non-recordable electroretinography. All harboured homozygous mutations in C21orf2, a gene recently suggested to be associated with retinal dystrophy but of unknown function. Two had a frameshift deletion c.436_466del (p.Glu146Serfs*6). The third had a missense mutation affecting a highly conserved residue (p.Cys61Tyr) and was short (below the 3rd percentile) and obese (50th percentile for weight despite short stature). Immunohistochemical studies in human, pig and mouse retinas localised C21orf2 protein to the ciliary structures of the photoreceptor cell (the daughter basal body, the centriole adjacent to the basal body, and the connecting cilium). CONCLUSIONS: This retinal dystrophy phenotype is caused by recessive mutations in C21orf2 and can be considered a retinal ciliopathy as C21orf2 encodes a protein that localises to photoreceptor ciliary structures. The short stature and obesity noted in the youngest girl suggest that for some patients biallelic C21orf2 mutations may result in syndromic ciliopathy.
Date of acceptance
2015
Autoren
  • Arif O Khan
  • Tobias Eisenberger
  • Kerstin Nagel-Wolfrum
  • Uwe Wolfrum
  • Hanno J Bolz
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/26294103
DOI
10.1136/bjophthalmol-2015-307277
eISSN
1468-2079
Ausgabe der Veröffentlichung
12
Zeitschrift
Br J Ophthalmol
Schlüsselwörter
  • Degeneration
  • Dystrophy
  • Genetics
  • Retina
  • Adult
  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Child
  • Consanguinity
  • Cytoskeletal Proteins
  • Dilatation, Pathologic
  • Electroretinography
  • Female
  • Frameshift Mutation
  • Genes, Recessive
  • Humans
  • Magnetic Resonance Imaging
  • Mice
  • Molecular Sequence Data
  • Mutation, Missense
  • Pedigree
  • Photoreceptor Connecting Cilium
  • Polymerase Chain Reaction
  • Proteins
  • Retina
  • Retinal Dystrophies
  • Retrospective Studies
  • Sus scrofa
  • Tissue Donors
  • Tomography, Optical Coherence
Sprache
eng
Country
England
Paginierung
1725 - 1731
PII
bjophthalmol-2015-307277
Datum der Veröffentlichung
2015
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2016
Titel
C21orf2 is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium.
Sub types
  • Case Reports
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
99

Data source: PubMed

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