epidermal-growth-factor and Retinitis-Pigmentosa

The purpose of this study was to investigate the genetic and clinical characteristics of eyes shut homolog (EYS)-associated retinitis pigmentosa (RP).. This was a retrospective cross-sectional observational study of 36 patients with EYS-associated autosomal recessive RP (arRP).. The gene sequencing results revealed that c.6416G>A (p.Cys2139Tyr) and c.7228+1G>A were the two most predominant variants in our cohort and that variants near the C-terminus, which contains alternating laminin and epidermal growth factor (EGF) domains, accounted for the majority of the allele counts (58 of a total of 72) and relative allele frequencies (81%). Over half of the patients presented with pericentral-type RP (n = 19, 60%), which frequently occurred in combination with macular lesions (n = 10, 52%). Patients having both variants within the alternating laminin and EGF domains near the C-terminus had a more severe disease progression (average 0.045 logMAR increase per year) than those having one variant in the N-terminus and the other in the C-terminus (average 0.001 logMAR increase per year).. Pericentral RP was the major phenotype in patients with EYS-associated arRP. There was also a statistically significant relationship between the location of the variants and the severity of the disease.. This study may aid patients with EYS-associated arRP to predict future vision acuity based on their genetic and clinical features.

Topics: Cross-Sectional Studies; DNA Mutational Analysis; Epidermal Growth Factor; Eye Proteins; Genes, Recessive; Genotype; Humans; Laminin; Mutation; Pedigree; Retinitis Pigmentosa; Retrospective Studies

Microdeletions Glu767(1-bp del), Thr967(1-bp del), and Leu1446(2-bp del) in the human USH2A gene have been reported to cause Usher syndrome type II, a disorder characterized by retinitis pigmentosa (RP) and mild-to-severe hearing loss. Each of these three frameshift mutations is predicted to lead to an unstable mRNA transcript that, if translated, would result in a truncated protein lacking the carboxy terminus. Here, we report Cys759Phe, a novel missense mutation in this gene that changes an amino-acid residue within the fifth laminin-epidermal growth factor-like domain of the USH2A gene and that is associated with recessive RP without hearing loss. This single mutation was found in 4.5% of 224 patients with recessive RP, suggesting that USH2A could cause more cases of nonsyndromic recessive RP than does any other gene identified to date.

Topics: Alleles; Amino Acid Sequence; Base Sequence; Deafness; Epidermal Growth Factor; Extracellular Matrix Proteins; Female; Genes, Recessive; Humans; Laminin; Male; Molecular Sequence Data; Mutation, Missense; Pedigree; Protein Structure, Tertiary; Retinitis Pigmentosa; Syndrome

Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.

Topics: Amino Acid Sequence; Animals; Cell Adhesion Molecules; Chromosome Mapping; Chromosomes, Human, Pair 1; Cochlea; Epidermal Growth Factor; Extracellular Matrix Proteins; Female; Fibronectins; Frameshift Mutation; Gene Expression; Genes, Recessive; Glycosylation; Hearing Loss, Sensorineural; Humans; Laminin; Male; Molecular Sequence Data; Pedigree; Retina; Retinitis Pigmentosa; Syndrome; Tumor Cells, Cultured