Human Molecular Genetics, 2003, Vol. 12, No. 9 1073-1078
DOI: 10.1093/hmg/ddg117
© 2003 Oxford University Press
Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination
1Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA and 2Department of Pediatrics, 3Department of Ophthalmology and 4Howard Hughes Medical Institute, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA
Received February 3, 2003; Revised February 24, 2003; Accepted March 2, 2003
Mutations in CRB1, the human homolog of Drosophila Crumbs, cause autosomal recessive blinding disorders of the retina. Whereas Crumbs is implicated in apical-basal epithelial polarity and photoreceptor morphogenesis, the role of CRB1 in normal or diseased retina remains unclear. We characterized the retinal organization in vivo of patients with CRB1 mutations and found that, unlike other inherited retinal degenerations studied to date, the CRB1 mutant retinas are remarkably thick in cross-section and lack the distinct layers of normal adult retina. There are coarse outer and inner zones and a thick surface layer around the optic nerve. The abnormal retinal architecture in CRB1 mutations resembles that of immature normal retina. The results suggest that the CRB1 disease pathway disturbs the development of normal human retinal organization by interrupting naturally occurring apoptosis.
* To whom correspondence should be addressed at: Scheie Eye Institute, University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA 19104, USA. Tel: +1 2156629981; Fax: +1 2156629388; Email: jacobsos{at}mail.med.upenn.edu
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