Mutations in RLBP1 associated with fundus albipunctatus in consanguineous Pakistani families

S Naz, S Ali, SA Riazuddin, T Farooq, NH Butt… - British journal of …, 2011 - bjo.bmj.com
S Naz, S Ali, SA Riazuddin, T Farooq, NH Butt, AU Zafar, SN Khan, T Husnain…
British journal of ophthalmology, 2011bjo.bmj.com
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 …
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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