Objective To identify disease-causing mutations in two consanguineous Pakistani families with fundus albipunctatus.
Methods Affected individuals in both families underwent a thorough clinical examination including funduscopy and electroretinography. Blood samples were collected from all participating members and genomic DNA was extracted. Exclusion analysis was completed with microsatellite short tandem repeat markers that span all reported loci for fundus albipunctatus. Two-point logarithm of odds (LOD) scores were calculated, and coding exons and exon–intron boundaries of RLBP1 were sequenced bi-directionally.
Results The ophthalmic examination of affected patients in both families was consistent with fundus albipunctatus. The alleles of markers on chromosome 15q flanking RLBP1 segregated with the disease phenotype in both families and linkage was further confirmed by two-point LOD scores. Bi-directional sequencing of RLBP1 identified a nonsense mutation (R156X) and a missense mutation (G116R) that segregated with the disease phenotype in their respective families.
Conclusions These results strongly suggest that mutations in RLBP1 are responsible for fundus albipunctatus in the affected individuals of these consanguineous Pakistani families.
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SN, SA, JFH and SR contributed equally to this study.
Funding This work was supported in part by Higher Education Commission, Islamabad, Pakistan and Ministry of Science and Technology, Islamabad, Pakistan.
Competing interests None to declare.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Institutional Review Board of National Centre of Excellence in Molecular Biology and the National Eye Institute.
Provenance and peer review Not commissioned; externally peer reviewed.