Journal article
A new locus for congenital cataract, microcornea, microphthalmia, and atypical iris coloboma maps to chromosome 2.
- Abouzeid H Jules-Gonin Eye Hospital, University of Lausanne, Switzerland.
- Meire FM
- Osman I
- ElShakankiri N
- Bolay S
- Munier FL
- Schorderet DF
- 2008-11-14
Published in:
- Ophthalmology. - 2009
Adolescent
Adult
Cataract
Child
Child, Preschool
Chromosome Mapping
Chromosomes, Human, Pair 2
Coloboma
Cornea
Crystallins
DNA Mutational Analysis
Eye Proteins
Female
Genetic Linkage
Haplotypes
Homeodomain Proteins
Humans
Iris
Lod Score
MafF Transcription Factor
Male
Microphthalmos
Microsatellite Repeats
Middle Aged
Nuclear Proteins
PAX6 Transcription Factor
Paired Box Transcription Factors
Pedigree
Repressor Proteins
English
OBJECTIVE
To report a novel phenotype of autosomal dominant atypical congenital cataract associated with variable expression of microcornea, microphthalmia, and iris coloboma linked to chromosome 2. Molecular analysis of this phenotype may improve our understanding of anterior segment development.
DESIGN
Observational case study, genome linkage analysis, and gene mutation screening.
PARTICIPANTS
Three families, 1 Egyptian and 2 Belgians, with a total of 31 affected were studied.
METHODS
Twenty-one affected subjects and 9 first-degree relatives underwent complete ophthalmic examination. In the Egyptian family, exclusion of PAX6, CRYAA, and MAF genes was demonstrated by haplotype analysis using microsatellite markers on chromosomes 11, 16, and 21. Genome-wide linkage analysis was then performed using 385 microsatellite markers on this family. In the 2 Belgian families, the PAX6 gene was screened for mutations by direct sequencing of all exons.
MAIN OUTCOME MEASURES
Phenotype description, genome-wide linkage of the phenotype, linkage to the PAX6, CRYAA, and MAF genes, and mutation detection in the PAX6 gene.
RESULTS
Affected members of the 3 families had bilateral congenital cataracts inherited in an autosomal dominant pattern. A novel form of hexagonal nuclear cataract with cortical riders was expressed. Among affected subjects with available data, 95% had microcornea, 39% had microphthalmia, and 38% had iris coloboma. Seventy-five percent of the colobomata were atypical, showing a nasal superior location in 56%. A positive lod score of 4.86 was obtained at theta = 0 for D2S2309 on chromosome 2, a 4.9-Mb common haplotype flanked by D2S2309 and D2S2358 was obtained in the Egyptian family, and linkage to the PAX6, CRYAA, or MAF gene was excluded. In the 2 Belgian families, sequencing of the junctions and all coding exons of PAX6 did not reveal any molecular change.
CONCLUSIONS
We describe a novel phenotype that includes the combination of a novel form of congenital hexagonal cataract, with variably expressed microcornea, microphthalmia, and atypical iris coloboma, not caused by PAX6 and mapping to chromosome 2.
FINANCIAL DISCLOSURE(S)
The authors have no proprietary or commercial interest in any materials discussed in this article.
To report a novel phenotype of autosomal dominant atypical congenital cataract associated with variable expression of microcornea, microphthalmia, and iris coloboma linked to chromosome 2. Molecular analysis of this phenotype may improve our understanding of anterior segment development.
DESIGN
Observational case study, genome linkage analysis, and gene mutation screening.
PARTICIPANTS
Three families, 1 Egyptian and 2 Belgians, with a total of 31 affected were studied.
METHODS
Twenty-one affected subjects and 9 first-degree relatives underwent complete ophthalmic examination. In the Egyptian family, exclusion of PAX6, CRYAA, and MAF genes was demonstrated by haplotype analysis using microsatellite markers on chromosomes 11, 16, and 21. Genome-wide linkage analysis was then performed using 385 microsatellite markers on this family. In the 2 Belgian families, the PAX6 gene was screened for mutations by direct sequencing of all exons.
MAIN OUTCOME MEASURES
Phenotype description, genome-wide linkage of the phenotype, linkage to the PAX6, CRYAA, and MAF genes, and mutation detection in the PAX6 gene.
RESULTS
Affected members of the 3 families had bilateral congenital cataracts inherited in an autosomal dominant pattern. A novel form of hexagonal nuclear cataract with cortical riders was expressed. Among affected subjects with available data, 95% had microcornea, 39% had microphthalmia, and 38% had iris coloboma. Seventy-five percent of the colobomata were atypical, showing a nasal superior location in 56%. A positive lod score of 4.86 was obtained at theta = 0 for D2S2309 on chromosome 2, a 4.9-Mb common haplotype flanked by D2S2309 and D2S2358 was obtained in the Egyptian family, and linkage to the PAX6, CRYAA, or MAF gene was excluded. In the 2 Belgian families, sequencing of the junctions and all coding exons of PAX6 did not reveal any molecular change.
CONCLUSIONS
We describe a novel phenotype that includes the combination of a novel form of congenital hexagonal cataract, with variably expressed microcornea, microphthalmia, and atypical iris coloboma, not caused by PAX6 and mapping to chromosome 2.
FINANCIAL DISCLOSURE(S)
The authors have no proprietary or commercial interest in any materials discussed in this article.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.ophtha.2008.08.044
- PMID 19004499
- Persistent URL
- https://sonar.ch/global/documents/20073
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