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author:("afar, Ahmad U")
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.  Ectopia Lentis in a Consanguineous Pakistani Family and a Novel Locus on Chromosome 8q 
Archives of Ophthalmology  2010;128(8):1046-1049.
Objective
To investigate the genetic basis and molecular characteristics of the isolated form of ectopia lentis.
Methods
We ascertained a consanguineous Pakistani family with multiple individuals with ectopia lentis. All affected as well as unaffected members with isolated ectopia lentis underwent detailed ophthalmologic and medical examination. Blood samples were collected and DNA was extracted. A genome-wide scan was completed with 382 polymorphic microsatellite markers, and logarithm of odds (LOD) scores were calculated.
Results
Maximum 2-point LOD scores of 5.68 and 2.88 at θ=0 were obtained for markers D8S285 and D8S260, respectively, during the genome-wide scan. Additional microsatellite markers refined the disease locus to a 16.96-cM (14.07-Mb) interval flanked by D8S1737 proximally and D8S1117 distally.
Conclusions
We report on a new locus for nonsyndromic autosomal recessive ectopia lentis on chromosome 8q11.23-q13.2 in a consanguineous Pakistani family.
Clinical Relevance
Identification of genetic loci and genes involved in ectopia lentis will enhance our understanding of the disease at a molecular level, leading to better genetic counseling and family screening and possible future development of better treatment.
doi:10.1001/archophthalmol.2010.165
PMCID: PMC3398798  PMID: 20697006
3.  Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family 
Molecular Vision  2010;16:511-517.
Purpose
To investigate the genetic basis of autosomal recessive congenital cataracts in a consanguineous Pakistani family.
Methods
All affected individuals underwent a detailed ophthalmological and clinical examination. Blood samples were collected and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic microsatellite markers. Logarithm of odds (LOD) scores were calculated, and Eph-receptor type-A2 (EPHA2), residing in the critical interval, was sequenced bidirectionally.
Results
The clinical and ophthalmological examinations suggested that all affected individuals have nuclear cataracts. Genome-wide linkage analyses localized the critical interval to a 20.78 cM (15.08 Mb) interval on chromosome 1p, with a maximum two-point LOD score of 5.21 at θ=0. Sequencing of EPHA2 residing in the critical interval identified a missense mutation: c.2353G>A, which results in an alanine to threonine substitution (p.A785T).
Conclusions
Here, we report for the first time a missense mutation in EPHA2 associated with autosomal recessive congenital cataracts.
PMCID: PMC2846848  PMID: 20361013
4.  Autosomal recessive congenital cataract in consanguineous Pakistani families is associated with mutations in GALK1 
Molecular Vision  2010;16:682-688.
Purpose
To identify the pathogenic mutations responsible for autosomal recessive congenital cataracts in consanguineous Pakistani families.
Methods
All affected individuals underwent detailed ophthalmologic and medical examination. Blood samples were collected and genomic DNA was extracted. A genome-wide scan was performed with polymorphic microsatellite markers on genomic DNA from affected and unaffected family members and logarithm of odds (LOD) scores were calculated. All coding exons of galactokinase (GALK1) were sequenced to identify pathogenic lesions.
Results
Clinical records and ophthalmological examinations suggested that affected individuals have nuclear cataracts. Linkage analysis localized the critical interval to chromosome 17q with a maximum LOD score of 5.54 at θ=0, with D17S785 in family PKCC030. Sequencing of GALK1, a gene present in the critical interval, identified a single base pair deletion: c.410delG, which results in a frame shift leading to a premature termination of GALK1: p.G137fsX27. Additionally, we identified a missense mutation: c.416T>C, in family PKCC055 that results in substitution of a leucine residue at position 139 with a proline residue: p.L139P, and is predicted to be deleterious to the native GALK1 structure.
Conclusions
Here, we report pathogenic mutations in GALK1 that are responsible for autosomal recessive congenital cataracts in consanguineous Pakistani families.
PMCID: PMC2855732  PMID: 20405025
5.  Mapping of a new locus associated with autosomal recessive congenital cataract to chromosome 3q 
Molecular Vision  2010;16:2634-2638.
Purpose
To localize the disease interval for autosomal recessive congenital cataracts in a consanguineous Pakistani family.
Methods
All affected individuals underwent detailed ophthalmologic examination. Blood samples were collected and genomic DNA was extracted. A genome-wide scan was performed with fluorescently-labeled microsatellite markers on genomic DNA from affected and unaffected family members and logarithm of odds (LOD) scores were calculated.
Results
Clinical records and ophthalmological examinations suggested that affected individuals have bilateral congenital cataracts. Genome-wide linkage analysis localized the critical interval to chromosome 3q with a maximum LOD score of 3.87 at θ=0; with marker D3S3609. Haplotype analyses refined the critical interval to a 23.39 cM (18.01 Mb) interval on chromosome 3q, flanked by D3S1614 proximally and D3S1262, distally.
Conclusions
Here, we report a new locus for autosomal recessive congenital cataract localized to chromosome 3q in a consanguineous Pakistani family.
PMCID: PMC3002966  PMID: 21179239
6.  Mapping of a novel locus associated with autosomal recessive congenital cataract to chromosome 8p 
Molecular Vision  2010;16:2911-2915.
Purpose
To identify the disease locus for autosomal recessive congenital cataracts in a consanguineous Pakistani family.
Methods
All affected individuals underwent a detailed ophthalmologic examination. Blood samples were collected and genomic DNA was extracted. A genome-wide scan was completed with fluorescently-labeled microsatellite markers on genomic DNA from affected and unaffected family members. Logarithms of odds (LOD) scores were calculated under a fully penetrant autosomal recessive model of inheritance.
Results
Ophthalmic examination suggested that affected individuals have bilateral cataracts. Linkage analysis localized the critical interval to chromosome 8p with LOD scores of 3.19, and 3.08 at θ=0, obtained with markers D8S549 and D8S550, respectively. Haplotype analyses refined the critical interval to 37.92 cM (16.28 Mb) region, flanked by markers, D8S277 proximally and D8S1734 distally.
Conclusions
Here, we report a new locus for autosomal recessive congenital cataract mapped to chromosome 8p in a consanguineous Pakistani family.
PMCID: PMC3013063  PMID: 21203409

Results 1-6 (6)