Further genetic heterogeneity for autosomal dominant human sutural cataracts.
A unique sutural cataract was observed in a 4-generation German family to be transmitted as an isolated autosomal, dominant trait. Since mutations in the gamma-crystallin encoding CRYG genes have previously been demonstrated to be the most frequent reason for isolated congenital cataracts, all 4 active CRYG genes have been sequenced. A single base-pair change in the CRYGA gene has been shown, leading to a premature stop codon. This was not observed in 170 control individuals. However, it did not segregate with the disease phenotype. This is the first truncating mutation in an active CRYG gene without a dominant phenotype. As the CRYGA mutation did not explain the cataract, several other candidate loci (CCV, GJA8, CRYBB2, BFSP2, MIP, GJA8, CENTRAL POUCH-LIKE, CRYBA1) were investigated by microsatellite markers and linkage analysis, but they were excluded based on the combination of haplotype analysis and two-point linkage analysis. The phenotype in this family is due to a mutation in another sutural cataract gene yet to be identified.
Klopp
Norman
N
GSF National Research Center for Environment and Health, Institutes of Developmental Genetics, Neuherberg, Germany.
Héon
Elise
E
Billingsley
Gail
G
Illig
Thomas
T
Wjst
Matthias
M
Rudolph
Günther
G
Graw
Jochen
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D025063:Chromosome Disorders; D003459:Crystallins / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
D003459:Crystallins; D005819:Genetic Markers; D004247:DNA