Homozygosity mapping identifies the Crumbs homologue 1 (Crb1) gene as responsible for a recessive syndrome of retinitis pigmentosa and nanophthalmos

Authors

  • Juan Carlos Zenteno,

    Corresponding author
    1. Faculty of Medicine, Department of Biochemistry, National Autonomous University of Mexico (UNAM), Mexico City, Mexico
    2. Department of Genetics-Research Unit, Institute of Ophthalmology “Conde de Valenciana,” Mexico City, Mexico
    • Department of Genetics, Institute of Ophthalmology “Conde de Valenciana,” Chimalpopoca 14, Col. Obrera, CP 06800, Mexico City, Mexico.
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  • Beatriz Buentello-Volante,

    1. Department of Genetics-Research Unit, Institute of Ophthalmology “Conde de Valenciana,” Mexico City, Mexico
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  • Raul Ayala-Ramirez,

    1. Department of Genetics-Research Unit, Institute of Ophthalmology “Conde de Valenciana,” Mexico City, Mexico
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  • Cristina Villanueva-Mendoza

    1. Department of Genetics, Hospital Dr. Luis Sanchez Bulnes, Asociación Para Evitar la Ceguera en México, Mexico City, Mexico
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  • How to Cite this Article: Zenteno JC, Buentello-Volante B, Ayala-Ramirez R, Villanueva-Mendoza C. 2011. Homozygosity mapping identifies the crumbs homologue 1 (Crb1) gene as responsible for a recessive syndrome of retinitis pigmentosa and nanophthalmos. Am J Med Genet Part A 155:1001–1006.

Abstract

The association of retinitis pigmentosa (RP) and microphthalmia has been reported in a number of familial and isolated cases. Here, the results of genetic analysis in a familial case of early RP associated with nanophthalmos are described. Two affected sibs were ascertained from an endogamous population in Mexico. A genome-wide linkage analysis was performed by means of an Affymetrix 250K microarray. Five large regions of homozygosity were demonstrated. The largest interval comprised 15.08 Mb at chromosome 1q31–32.1 and contained the Crumbs homologue-1, CRB1, a gene responsible for a number of recessive retinal dystrophies. Nucleotide sequence analysis demonstrated a c.1125C>G transversion in CRB1 exon 5, predicting a novel p.Tyr375X variant. To our knowledge this is the first instance in which a CRB1 mutation has been associated with early RP and nanophthalmos. Our results suggest a role for CRB1 in promoting axial growth of the eye. Clinical analysis of additional subjects with retinal dystrophies due to CRB1 mutations will help to identify if the high hyperopia, a frequently observed trait in these subjects, could be related to decreased eye axial length (nanophthalmos). © 2011 Wiley-Liss, Inc.

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