A new locus for autosomal dominant cataract on chromosome 19: linkage analyses and screening of candidate genes.
OBJECTIVE
To map and identify the mutated gene for autosomal dominant cataract (ADC) in family ADC4.


METHODS
Ophthalmic evaluations were performed on an American family with ADC and a panel of polymorphic DNA sequence-tagged site (STS) markers for known ADC loci and other genome-wide polymorphic markers were used to map the gene; two-point lod scores were calculated. Fine mapping was undertaken in the chromosomal regions of maximum lod scores, and candidate genes were sequenced.


RESULTS
A four-generation American family with ADC was studied. The only phakic individual exhibited white and vacuolated opacities in the cortical region. This ADC locus mapped to several suggestive chromosomal regions. Assuming full penetrance, the highest calculated maximum lod score was 3.91 with D19S903 [corrected] On chromosome 12, we sequenced all exons and the exon-intron borders of the membrane intrinsic protein (MIP) gene. On chromosome 19, all exons and the exon-intron borders of genes for lens intrinsic membrane2 (LIM2), ferritin light chain (FTL), and the human homologue of the Drosophila sine oculis homeobox 5 (SIX5) were sequenced, and the 3' untranslated repeat region (UTR) of the dystrophy (DMPK) gene and both the 5' and 3' UTRs of the SIX5 genes were amplified; the promoter for LIM2 was sequenced. For these genes, the sequence matched that in the reference libraries, and the DMPK gene had a normal number of CTG repeats.


CONCLUSIONS
The mutated gene in ADC4 probably represents a new, not yet identified locus on chromosome 19. In one phakic member, the cortical cataracts were punctate and vacuolated.
Bateman
J Bronwyn
JB
Department of Ophthalmology, Rocky Mountain Lions Eye Institute, Denver, CO 80045, USA. bronwyn.bateman@uchsc.edu
Richter
Leslie
L
Flodman
Pamela
P
Burch
Douglas
D
Brown
Sandra
S
Penrose
Philip
P
Paul
Otis
O
Geyer
David D
DD
Brooks
David G
DG
Spence
M Anne
MA
D002386:Cataract / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D005820:Genetic Testing; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction
D005819:Genetic Markers