Dataset Information

Primary congenital glaucoma localizes to chromosome 14q24.2-24.3 in two consanguineous Pakistani families.

ABSTRACT:

Purpose

Two consanguineous Pakistani families with autosomal recessive primary congenital glaucoma were recruited to identify the disease locus.

Methods

Ophthalmic examinations including slit lamp biomicroscopy and applanation tonometry were employed to classify the phenotype. Blood samples were collected and genomic DNA was extracted. A genome wide scan was performed on both families with 382 polymorphic microsatellite markers. Two point LOD scores were calculated, and haplotypes were constructed to define the disease interval.

Results

Clinical records and ophthalmic examinations suggest that affected individuals in families PKGL005 and PKGL025 have primary congenital glaucoma. Maximum two-point LOD scores of 5.88 with D14S61 at theta=0 and 6.19 with D14S43 at theta=0 were obtained for families PKGL005 and PKGL025, respectively. Haplotype analysis defined the disease locus as spanning a 6.56 cM (~4.2 Mb) genetic interval flanked by D14S289 proximally and D14S85 distally.

Conclusions

Linkage analysis localizes autosomal recessive primary congenital glaucoma to chromosome 14q24.2-24.3 in consanguineous Pakistani families.

SUBMITTER: Firasat S

PROVIDER: S-EPMC2530517 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Publications

Primary congenital glaucoma localizes to chromosome 14q24.2-24.3 in two consanguineous Pakistani families.

Firasat Sabika S Riazuddin S Amer SA Hejtmancik J Fielding JF Riazuddin Sheikh S

Molecular vision 20080905

<h4>Purpose</h4>Two consanguineous Pakistani families with autosomal recessive primary congenital glaucoma were recruited to identify the disease locus.<h4>Methods</h4>Ophthalmic examinations including slit lamp biomicroscopy and applanation tonometry were employed to classify the phenotype. Blood samples were collected and genomic DNA was extracted. A genome wide scan was performed on both families with 382 polymorphic microsatellite markers. Two point LOD scores were calculated, and haplotypes ...[more]

PMID: 18776954

Similar Datasets

Project description:BackgroundPrimary congenital glaucoma (PCG) is a heterogeneous rare recessively inherited disorder prevalent in regions with high consanguinity. Disease phenotype is associated with increased intra ocular pressure and is a major cause of childhood blindness. Sequence variations in Cytochrome P450 1B1 (CYP1B1) gene are a major cause of PCG. Current study was conducted to screen CYP1B1 gene in highly consanguineous PCG affected families from Pakistani population consistent with the autosomal recessive pattern of PCG inheritance.MethodsFor this study, patients and controls (clinically unaffected individuals of each family) from 25 consanguineous families belonging to Punjab, Baluchistan and Khyber Pakhtunkhwa, Pakistan were recruited through ophthalmologists. DNA was isolated from collected blood samples. Genetic screening of CYP1B1 gene was done for all enrolled families. In-silico analysis was performed to identify and predict the potential disease-causing variations.ResultsPathogenicity screening revealed sequence variants segregating with disease phenotype in homozygous or compound heterozygous form in eleven out of 25 analyzed families. We identified a total of sixteen disease causing variants among which five frameshift i.e., c.629dup (p.Gly211Argfs*13), c.287dup (p.Leu97Alafs*127), c.662dup (p.Arg222Profs*2), c.758_759insA (p.Val254Glyfs*73) and c.789dup (p.Leu264Alafs*63), two silent c.1314G>A, c.771T>G and six missense variations c.457C>G (p.Arg153Gly), c.516C>A (p.Ser172Arg), c.722T>A (p.Val241Glu), c.740T>A (p.Leu247Gln), c.1263T>A (p.Phe421Leu), and c.724G>C (p.Asp242His) are previously un reported. However two frameshift c.868dup (p.Arg290Profs*37), c.247del (p.Asp83Thrfs*12) and one missense variant c.732G>A (p.Met244Ile), is previously reported. Furthermore, six polymorphisms c.1347T>C, c.2244_2245insT, c.355G>T, c.1294G>C, c.1358A>G and c.142C>G were also identified. In the intronic region, a novel silent polymorphism i.e., g.35710_35711insT was found in homozygous state. All the newly detected disease-causing variants were negative in 96 ethnically matched controls.ConclusionAmong twenty-five screened families, eight families (PCG50, 52-54, 58, 59, 63 and 67) were segregating disease causing variants in recessive manner. Two families (PCG049 and PCG062) had compound heterozygosity. Our data confirms genetic heterogeneity of PCG in Pakistani population however we did not find molecular variants segregating with PCG in fifteen families in coding exons and intron-exon boundaries of CYP1B1 gene. Genetic counseling was provided to families to refrain from practicing consanguinity and perform premarital screening as a PCG control measure in upcoming generations.

Dataset Information

Primary congenital glaucoma localizes to chromosome 14q24.2-24.3 in two consanguineous Pakistani families.

Purpose

Methods

Results

Conclusions

Publications

Primary congenital glaucoma localizes to chromosome 14q24.2-24.3 in two consanguineous Pakistani families.

Similar Datasets

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