LETTER TO JMG

A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population

S Yzer^1,2, L I van den Born¹, J Schuil³, H Y Kroes⁴, M M van Genderen³, F N Boonstra³, B van den Helm², H G Brunner², R K Koenekoop⁵, F P M Cremers²

¹ The Rotterdam Eye Hospital, Rotterdam, Netherlands
² Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, Netherlands
³ Institute for the Visually Handicapped "Bartimeus", Zeist, Netherlands
⁴ Department of Medical Genetics, University Medical Centre Utrecht, Netherlands
⁵ The McGill Ocular Genetics Laboratory, Montreal Children’s Hospital Research Institute, McGill University Montreal, Canada

Correspondence to:
Correspondence to:
Dr F P M Cremers Department of Human Genetics, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands;
f.cremers@antrg.umcn.nl

Keywords: early onset retinal dystrophy; RPE65 founder mutation; carrier frequency; genetic isolate

The first 150 words of the full text of this article appear below.

Autosomal recessive retinal dystrophies cause visual impairment in approximately 1 in 4000 individuals worldwide.¹ The non-syndromic forms are highly heterogeneous and can be classified into clinical subgroups, the most frequent ones being retinitis pigmentosa, cone and cone-rod dystrophies, and Leber congenital amaurosis (LCA). LCA represents the most severe phenotype with an onset of symptoms before the age of six months, visual acuity below 20/400, a searching nystagmus, sluggish pupillary reactions, and a non-detectable electroretinogram (ERG). Visual fields are usually not measurable.¹ Photophobia is only occasionally reported in LCA.² Patients with juvenile and early onset retinitis pigmentosa present with night blindness in early childhood, usually before the age of two years. They do not show searching nystagmus³ and have a relatively well preserved macular function. Central vision is often lost in the second or third decade of life.⁴

The cloning of more than 20 genes allows the molecular characterisation of approximately . . . [Full text of this article]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Lorenz, B., Poliakov, E., Schambeck, M., Friedburg, C., Preising, M. N., Redmond, T. M. (2008). A Comprehensive Clinical and Biochemical Functional Study of a Novel RPE65 Hypomorphic Mutation. IOVS 49: 5235-5242 [Abstract] [Full Text]  
• Yzer, S., Fishman, G. A., Racine, J., Al-Zuhaibi, S., Chakor, H., Dorfman, A., Szlyk, J., Lachapelle, P., van den Born, L. I., Allikmets, R., Lopez, I., Cremers, F. P. M., Koenekoop, R. K. (2006). CRB1 Heterozygotes with Regional Retinal Dysfunction: Implications for Genetic Testing of Leber Congenital Amaurosis.. IOVS 47: 3736-3744 [Abstract] [Full Text]  
• Takahashi, Y., Chen, Y., Moiseyev, G., Ma, J.-x. (2006). Two Point Mutations of RPE65 from Patients with Retinal Dystrophies Decrease the Stability of RPE65 Protein and Abolish Its Isomerohydrolase Activity. J. Biol. Chem. 281: 21820-21826 [Abstract] [Full Text]  
• Yzer, S., Leroy, B. P., De Baere, E., de Ravel, T. J., Zonneveld, M. N., Voesenek, K., Kellner, U., Ciriano, J. P. M., de Faber, J.-T. H. N., Rohrschneider, K., Roepman, R., den Hollander, A. I., Cruysberg, J. R., Meire, F., Casteels, I., van Moll-Ramirez, N. G., Allikmets, R., van den Born, L. I., Cremers, F. P. M. (2006). Microarray-based mutation detection and phenotypic characterization of patients with leber congenital amaurosis.. IOVS 47: 1167-1176 [Abstract] [Full Text]  
• Jacobson, S. G., Aleman, T. S., Cideciyan, A. V., Sumaroka, A., Schwartz, S. B., Windsor, E. A. M., Traboulsi, E. I., Heon, E., Pittler, S. J., Milam, A. H., Maguire, A. M., Palczewski, K., Stone, E. M., Bennett, J. (2005). Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success. Proc. Natl. Acad. Sci. USA 102: 6177-6182 [Abstract] [Full Text]