title: Homozygosity mapping identifies the Crumbs homologue 1 (Crb1) gene as responsible for a recessive syndrome of retinitis pigmentosa and nanophthalmos.
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).
authors.affiliation: Faculty of Medicine, Department of Biochemistry, National Autonomous University of Mexico, Mexico City, Mexico. jczenteno@institutodeoftalmologia.org
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zenteno
authors.forename: Beatriz
authors.initials: B
authors.lastname: Buentello-Volante
authors.forename: Raul
authors.initials: R
authors.lastname: Ayala-Ramirez
authors.forename: Cristina
authors.initials: C
authors.lastname: Villanueva-Mendoza
mesh_terms: D000328:Adult; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008850:Microphthalmos / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins