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Raul Ayala Ramirez, Beatriz Buentello-Volante, Cristina Villanueva-Mendoza, Juan Carlos Zenteno; Genome-wide Homozygosity Mapping With SNP Microarrays Identifies The Crumbs Homologue 1 (CRB1) Gene As Responsible For A Recessive Syndrome Of Retinitis Pigmentosa And Nanophthalmos. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2373.
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The clinical association of retinitis pigmentosa 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 retinitis pigmentosa associated with nanophthalmos are described.
Two affected sibs were ascertained from an endogamous population in Mexico. A genome wide linkage analysis was performed on DNA from both sibs by means of an Affymetrix 250K single-nucleotide polymorphism microarray. Significant homozygous regions shared by the affected patients were identified using the HomozygosityMapper software, and candidate genes were searched by GeneDistiller software.
Five large regions of homozygosity were demonstrated. The largest interval comprised 15.08 MB at chromosome 1q31-q32.1 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 nonsense mutation at the protein level.
To our knowledge this is the first instance in which a CRB1 mutation results in the clinical association of early retinitis pigmentosa and nanophthalmos. Our results suggest a role for CRB1 in promoting eye axial growth. Detailed 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).
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