Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase.

Choroideremia (CHM), an X-linked degeneration of the retinal pigmented epithelium (RPE), photoreceptors, and choroid, ultimately leads to blindness. It is caused by loss-of-function of the CHM gene product, the Rab escort protein 1 (REP1) that is involved, together with its homologue REP2, in prenylation of Rab GTPases, key regulators of intracellular vesicular traffic. Here, we report the molecular characterization of 20 unrelated Italian families affected by CHM.

Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

Purpose: To identify the molecular basis of Leber's congenital amaurosis (LCA) in a cohort of Italian patients and to perform genotype-phenotype analysis.

Methods: DNA samples from 95 patients with LCA were analyzed by using a microarray chip containing disease-associated sequence variants in eight LCA genes. In addition, all patients in whom no mutations were identified by microarray were subjected to sequence analysis of the CEP290 gene.

Genotype-phenotype correlation in Italian families with Stargardt disease.

Autosomal recessive Stargardt disease (STGD) has been associated with substantial genetic and phenotypic heterogeneity. By systematic clinical analyses of STGD patients with complete genetic data (i.e.

Association of a homozygous nonsense mutation in the ABCA4 (ABCR) gene with cone-rod dystrophy phenotype in an Italian family.

Genetic variation in the ABCA4 (ABCR) gene has been associated with several distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), retinitis pigmentosa (RP) and age-related macular degeneration. The current model of genotype/phenotype association suggests that patients harboring deleterious mutations in both ABCR alleles would develop RP-like retinal pathology. Here we describe ABCA4-associated phenotypes, including a proband with a homozygous nonsense mutation in a family from Southern Italy.

Identification and characterization of C1orf36, a transcript highly expressed in photoreceptor cells, and mutation analysis in retinitis pigmentosa.

By means of computational methods, we identified an uncharacterized human transcript, Chromosome 1 open reading frame 36 (C1orf36), that is expressed in the retina and that maps to 1q32.3. The cDNA contains an open reading frame of 585bp that encodes a 195-aminoacid protein with a predicted mass of 22.

Characterization of MPP4, a gene highly expressed in photoreceptor cells, and mutation analysis in retinitis pigmentosa.

Membrane-associated guanylate kinase (MAGUK) proteins are cell-cell contact organizing molecules that mediate targeting, clustering and anchoring of proteins at synapses and other cell junctions. MAGUK proteins may contain multiple protein-protein interaction motifs including PDZ, SH3 and guanylate kinase (GuK) domains. In this study, we performed a detailed analysis of the expression pattern of MPP4, a recently described member of the MAGUK protein family.

An Italian family affected by autosomal dominant microcephaly with chorioretinal degeneration.

Purpose: We studied an Italian family affected by the autosomal dominant form of microcephaly and chorioretinal degeneration that was characterized by various degrees of clinical expression.

Methods: An ophthalmologic examination, including visual acuity, visual field testing, an electroretinogram, and fundus photography, and a neurologic examination, including neurodevelopmental status and neuroimaging studies, were performed for all subjects. Skeletal radiography, chromosome studies, and serologic investigations were also performed.