Dataset Information

Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa.

ABSTRACT: PURPOSE: To describe two novel mutations in the eyes shut homolog (EYS) gene in two families with autosomal recessive retinitis pigmentosa (arRP) from Pakistan and Indonesia. METHODS: Genome-wide linkage and homozygosity mapping were performed using single nucleotide polymorphism microarray analysis in affected members of the two arRP families. Sequence analysis was performed to identify genetic changes in protein coding exons of EYS. RESULTS: In the Indonesian and Pakistani families, homozygous regions encompassing the EYS gene at 6q12 were identified, with maximum LOD scores of 1.8 and 3.6, respectively. Novel missense variants in the EYS gene (p.D2767Y and p.D3028Y) were found in the Pakistani and Indonesian families, respectively, that co-segregate with the disease phenotype. Interestingly, the missense variants are located at the same homologous position within the fourth and fifth laminin A G-like domains of EYS. CONCLUSIONS: To date, mostly protein-truncating mutations have been described in EYS, while only few patients have been described with pathogenic compound heterozygous missense mutations. The mutations p.D2767Y and p.D3028Y described in this study affect highly conserved residues at homologous positions in laminin A G-like domains and support the notion that missense mutations in EYS can cause arRP.

SUBMITTER: Khan MI

PROVIDER: S-EPMC3003713 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa.

Khan Muhammad Imran MI Collin Rob W J RW Arimadyo Kentar K Micheal Shazia S Azam Maleeha M Qureshi Nadeem N Faradz Sultana M H SM den Hollander Anneke I AI Qamar Raheel R Cremers Frans P M FP

Molecular vision 20101215

<h4>Purpose</h4>To describe two novel mutations in the eyes shut homolog (EYS) gene in two families with autosomal recessive retinitis pigmentosa (arRP) from Pakistan and Indonesia.<h4>Methods</h4>Genome-wide linkage and homozygosity mapping were performed using single nucleotide polymorphism microarray analysis in affected members of the two arRP families. Sequence analysis was performed to identify genetic changes in protein coding exons of EYS.<h4>Results</h4>In the Indonesian and Pakistani f ...[more]

PMID: 21179430

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Project description:PURPOSE: Retinitis pigmentosa (RP; MIM 268000) is a hereditary disease characterized by poor night vision and progressive loss of photoreceptors, eventually leading to blindness. This degenerative process primarily affects peripheral vision due to the loss of rods. Autosomal recessive RP (arRP) is clinically and genetically heterogeneous. It has been associated with mutations in different genes, including CRB1 (crumbs homolog 1). The aim of this study was to determine the causative gene in a Tunisian patient with arRP born to non-consanguineous parents. METHODS: Four accessible family members were included. They underwent full ophthalmic examination with best-corrected Snellen visual acuity, fundus photography and fluorescein angiography. Haplotype analysis was used to evaluate homozygosity in the family to 20 arRP loci. All exons and intron-exon junctions of candidate genes not excluded by haplotype analysis were PCR amplified and directly sequenced. RESULTS: The proband was a 43-year-old female patient. Best-corrected visual acuity was 20/63 (right eye) and 20/80 (left eye). Visual loss began during the third decade. Funduscopic examination and fluorescein angiography revealed typical advanced RP changes with bone spicule-like pigment deposits in the posterior pole and the midperiphery along with retinal atrophy, narrowing of the vessels, and waxy optic discs. Haplotype analysis revealed homozygosity with microsatellite markers D1S412 and D1S413 on chromosome 1q31.3. These markers flanked CRB1. Our results excluded linkage of all the other arRP loci/genes tested. Sequencing of the 12 coding exons and splice sites of CRB1 disclosed a homozygous missense mutation in exon 7 at nucleotide c. 2291G>A, resulting in an arginine to histidine substitution (p.R764H). CONCLUSIONS: R764H is a novel mutation associated with CRB1-related arRP. Previously, an R764C mutation was reported. Extending the mutation spectrum of CRB1 with additional families is important for genotype-phenotype correlations and characterization of the scope of mutation.

Dataset Information

Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa.

Publications

Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa.

Similar Datasets

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