Universität zu Köln

Khan, Arif O., Eisenberger, Tobias, Nagel-Wolfrum, Kerstin, Wolfrum, Uwe and Bolz, Hanno J. (2015). C21orf2 is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium. Br. J. Ophthalmol., 99 (12). S. 1725 - 1732. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2079

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Khan, Arif O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eisenberger, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagel-Wolfrum, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolfrum, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolz, Hanno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-385543
DOI:	10.1136/bjophthalmol-2015-307277
Journal or Publication Title:	Br. J. Ophthalmol.
Volume:	99
Number:	12
Page Range:	S. 1725 - 1732
Date:	2015
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-2079
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ROD-CONE DYSTROPHY; POSTERIOR STAPHYLOMA; CILIARY; CILIOPATHY; REGULATORS; MUTATIONS; CATARACT; CHILDREN; GENES; CELLS Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38554