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Nonsense mutation in the CRYBB2 gene causing autosomal dominant progressive polymorphic congenital coronary cataracts.

Li FF, Zhu SQ, Wang SZ, Gao C, Huang SZ, Zhang M, Ma X - Mol. Vis. (2008)

Bottom Line: All members were genotyped with microsatellite markers at loci previously associated with cataracts.This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals.These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

View Article: PubMed Central - PubMed

Affiliation: Graduate School, Peking Union Medical College, Beijing, China.

ABSTRACT

Purpose: We sought to identify the genetic defect in a large, five-generation Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts and to examine the clinical features in detail.

Methods: Clinical and ophthalmologic examinations were conducted on family members. All members were genotyped with microsatellite markers at loci previously associated with cataracts. Two-point LOD scores were calculated using a linkage package after genotyping. A mutation was detected by direct sequencing and verified by denaturing high-performance liquid chromatography (DHPLC).

Results: Clinical observations showed that all affected family members had progressive polymorphic coronary cataracts. Linkage analysis was obtained at markers, D22S303 (LOD score [Z]=2.11, recombination fraction [theta]=0.0) and D22S1167 (Z=1.20, theta=0.0). Haplotype analysis indicated that the cataract gene was closely linked with these two markers. Sequencing the betaB-crystallin gene (CRYBB2) revealed a C --> T transition in exon 6, which changed a codon from Gln to a stop codon (P.Q155X). This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals.

Conclusions: This study identified a mutation in CRYBB2 in a large Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts. These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

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Related in: MedlinePlus

Pedigree and haplotype of the cataract family. Five-generation pedigree segregates autosomal dominant progressive polymorphic coronary cataracts. Haplotyping showed segregation with two microsatellite markers on 22q. Squares and circles indicate males and females, respectively. Blackened symbols and bars denote affected status.
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f2: Pedigree and haplotype of the cataract family. Five-generation pedigree segregates autosomal dominant progressive polymorphic coronary cataracts. Haplotyping showed segregation with two microsatellite markers on 22q. Squares and circles indicate males and females, respectively. Blackened symbols and bars denote affected status.

Mentions: The CRYBB2 gene on chromosome 22 was linked to this family’s disease while other candidate genes were excluded by allele sharing and linkage analysis. Significant linkage was found with markers, D22S303 and D22S1167; the maximum LOD score was 2.11 (at θ=0). Haplotype analysis showed that the phenotype was localized at chromosome 22q11.2–12.2 flanked by markers, D22S303 and D22S1167 (Figure 2, Table 2).


Nonsense mutation in the CRYBB2 gene causing autosomal dominant progressive polymorphic congenital coronary cataracts.

Li FF, Zhu SQ, Wang SZ, Gao C, Huang SZ, Zhang M, Ma X - Mol. Vis. (2008)

Pedigree and haplotype of the cataract family. Five-generation pedigree segregates autosomal dominant progressive polymorphic coronary cataracts. Haplotyping showed segregation with two microsatellite markers on 22q. Squares and circles indicate males and females, respectively. Blackened symbols and bars denote affected status.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2335123&req=5

f2: Pedigree and haplotype of the cataract family. Five-generation pedigree segregates autosomal dominant progressive polymorphic coronary cataracts. Haplotyping showed segregation with two microsatellite markers on 22q. Squares and circles indicate males and females, respectively. Blackened symbols and bars denote affected status.
Mentions: The CRYBB2 gene on chromosome 22 was linked to this family’s disease while other candidate genes were excluded by allele sharing and linkage analysis. Significant linkage was found with markers, D22S303 and D22S1167; the maximum LOD score was 2.11 (at θ=0). Haplotype analysis showed that the phenotype was localized at chromosome 22q11.2–12.2 flanked by markers, D22S303 and D22S1167 (Figure 2, Table 2).

Bottom Line: All members were genotyped with microsatellite markers at loci previously associated with cataracts.This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals.These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

View Article: PubMed Central - PubMed

Affiliation: Graduate School, Peking Union Medical College, Beijing, China.

ABSTRACT

Purpose: We sought to identify the genetic defect in a large, five-generation Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts and to examine the clinical features in detail.

Methods: Clinical and ophthalmologic examinations were conducted on family members. All members were genotyped with microsatellite markers at loci previously associated with cataracts. Two-point LOD scores were calculated using a linkage package after genotyping. A mutation was detected by direct sequencing and verified by denaturing high-performance liquid chromatography (DHPLC).

Results: Clinical observations showed that all affected family members had progressive polymorphic coronary cataracts. Linkage analysis was obtained at markers, D22S303 (LOD score [Z]=2.11, recombination fraction [theta]=0.0) and D22S1167 (Z=1.20, theta=0.0). Haplotype analysis indicated that the cataract gene was closely linked with these two markers. Sequencing the betaB-crystallin gene (CRYBB2) revealed a C --> T transition in exon 6, which changed a codon from Gln to a stop codon (P.Q155X). This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals.

Conclusions: This study identified a mutation in CRYBB2 in a large Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts. These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

Show MeSH
Related in: MedlinePlus