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1.  Mutations in RLBP1 associated with fundus albipunctatus in consanguineous Pakistani families 
The British journal of ophthalmology  2011;95(7):1019-1024.
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.
doi:10.1136/bjo.2010.189076
PMCID: PMC3459316  PMID: 21447491
2.  Nonsense mutation in MERTK causes autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family 
The British Journal of Ophthalmology  2010;94(8):1094-1099.
Background
Retinitis pigmentosa (RP) is one of the most common ophthalmic disorders affecting one in approximately 5000 people worldwide. A nuclear family was recruited from the Punjab province of Pakistan to study the genetic basis of autosomal recessive RP.
Methods
All affected individuals underwent a thorough ophthalmic examination and the disease was characterised based upon results for fundus photographs and electroretinogram recordings. Genomic DNA was extracted from peripheral leucocytes. Exclusion studies were performed with short tandem repeat (STR) markers flanking reported autosomal recessive RP loci. Haplotypes were constructed and results were statistically evaluated.
Results
The results of exclusion analyses suggested that family PKRP173 was linked to chromosome 2q harbouring mer tyrosine kinase protooncogene (MERTK), a gene previously associated with autosomal recessive RP. Additional STR markers refined the critical interval and placed it in a 13.4 cM (17 Mb) region flanked by D2S293 proximally and D2S347 distally. Significant logarithm of odds (LOD) scores of 3.2, 3.25 and 3.18 at θ=0 were obtained with markers D2S1896, D2S2269 and D2S160. Sequencing of the coding exons of MERTK identified a mutation, c.718G→T in exon 4, which results in a premature termination of p.E240X that segregates with the disease phenotype in the family.
Conclusion
Our results strongly suggest that the nonsense mutation in MERTK, leading to premature termination of the protein, is responsible for RP phenotype in the affected individuals of the Pakistani family.
doi:10.1136/bjo.2009.171892
PMCID: PMC3393880  PMID: 20538656
3.  Clinical and genetic features in Italian Bietti crystalline dystrophy patients 
Aim
The aim of the study was to describe the clinical and genetic features of 15 Italian patients with Bietti crystalline dystrophy (BCD).
Methods
All study participants underwent a complete ophthalmological examination, including standard electroretinogram (ERG), optical coherence tomography, microperimetry, autofluorescence and multifocal electroretinogram. The 11 exons of the CYP4V2 gene were sequenced. The effect of mutations on protein function was estimated by a combination of web based programs.
Results
15 patients (eight women, 7 men, aged 29–60 years) with BCD were recruited into this study. Sequencing of CYP4V2 revealed nine sequence variants in four unrelated families and six isolated individuals with BCD. Seven of these variants were novel. Among the patients, even with the same genotype, considerable variability in phenotypic expression with different degrees of accumulation of the typical intraretinal crystalline deposits was detected. Moreover, we found that more than 50% of patients had recordable standard ERG responses and in two patients the responses were within normal limits after 20 years of symptom onset.
Conclusions
In conclusion, we have reported seven new mutations and illustrated the large range of genotypic and phenotypic variability in BCD, highlighting the lack of a clear genotype–phenotype correlation and underlining the existence of less severe clinical manifestations, probably linked to relatively mild mutations.
doi:10.1136/bjophthalmol-2012-302469
PMCID: PMC3582089  PMID: 23221965
Retina; Genetics; Degeneration

Results 1-3 (3)