Nature Genetics
22, 199 - 202 (1999)
doi:10.1038/9722
A single EFEMP1 mutation associated with both Malattia Leventinese
and Doyne honeycomb retinal dystrophyEdwin M. Stone1, Andrew J. Lotery1, Francis L. Munier2, 3, Elise Héon4, 5, Bertrand Piguet2, Robyn H. Guymer6, Kimberlie Vandenburgh1, Pascal Cousin2, Darryl Nishimura7, Ruth E. Swiderski7, Giuliana Silvestri8, David A. Mackey6, 9, Gregory S. Hageman1, Alan C. Bird10, Val C. Sheffield7, 11
& Daniel F. Schorderet31
The Department of Ophthalmology, The University of
Iowa College of Medicine, Iowa City, USA. 2
Hôpital Jules Gonin, Lausanne,
Switzerland. 3
Division de Génétique Médicale,
CHUV, Lausanne, Switzerland. 4
The Department of Ophthalmology, University of Toronto
, Toronto, Canada
5
Eye Research Institute of Canada, Toronto
, Canada. 6
Centre for Eye Research Australia, The University of
Melbourne, Royal Victorian Eye and Ear Hospital, Victoria,
Australia. 7
The Department of Pediatrics, The University of Iowa
College of Medicine, Iowa City, Iowa, USA.
8
The Department of Ophthalmology, Royal Victoria Hospital
, Belfast, Northern Ireland. 9
Menzies Centre for Population Health Research, The
University of Tasmania, Tasmania, Australia. 10
The Institute of Ophthalmology, Moorfields Eye Hospital
, London, England. 11
The Howard Hughes Medical Institute, University of
Iowa, Iowa City, Iowa, USA..
Correspondence should be addressed to Edwin M. Stone edwin-stone@uiowa.edu or Francis L. Munier francis.munier@chuv.hospvd.ch or Val C. Sheffield val-sheffield@uiowa.eduMalattia Leventinese (ML) and Doyne honeycomb retinal dystrophy (DHRD)
refer to two autosomal dominant diseases characterized by yellow-white deposits
known as drusen that accumulate beneath the retinal pigment epithelium1,
2,
3,
4 (RPE). Both loci were mapped to chromosome 2p16-21 (Refs 5,6) and this genetic interval
has been subsequently narrowed6,
7. The importance of these
diseases is due in large part to their close phenotypic similarity to age-related
macular degeneration (AMD), a disorder with a strong genetic component8,
10 that accounts for approximately 50% of registered blindness
in the Western world11,
12,
13,
14. Just as in ML and DHRD,
the early hallmark of AMD is the presence of drusen15,
16. Here
we use a combination of positional and candidate gene methods to identify
a single non-conservative mutation (Arg345Trp) in the gene EFEMP1 (for
EGF-containing fibrillin-like extracellular matrix protein 1) in all families
studied. This change was not present in 477 control individuals or in 494
patients with age-related macular degeneration. Identification of this mutation
may aid in the development of an animal model for drusen, as well as in the
identification of other genes involved in human macular degeneration.
|
