A family with autosomal dominant primary congenital cataract associated with a CRYGC mutation: evidence of clinical heterogeneity.
OBJECTIVE
To describe a family with primary congenital cataract associated with a CRYGC mutation.


METHODS
One family with several affected members with primary congenital cataract and 170 healthy controls were examined. DNA from leukocytes was isolated to analyze the CRYGA-D gene cluster.


RESULTS
DNA sequencing analysis of the CRYGA-D gene cluster of the affected members showed the heterozygous missense mutation c.502C>T in the CRYGC gene. This transition mutation resulted in the substitution of Arg at position 168 by Trp. Analysis of the healthy members of the family and 170 unrelated controls showed a normal sequence of the CRYGA-D gene cluster.


CONCLUSIONS
In the present study, we described a family with nuclear congenital cataract that segregated the CRYGC missense mutation c.502C>T. This mutation has been associated with the phenotype of lamellar cataract but is also considered a single nucleotide polymorphism (SNP) in the NCBI database. Our data and previous report support that R168W is the actual disease-causing mutation and should no longer be considered a SNP. This is the first case of phenotypic heterogeneity in the primary congenital cataract specifically associated with the R168W mutation in the CRYGC gene.
Department of Genetics, General Hospital of Mexico, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Luz M
LM
Gonzalez-Huerta
Olga M
OM
Messina-Baas
Sergio A
SA
Cuevas-Covarrubias
D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016415:Sequence Alignment; D038222:gamma-Crystallins / Q000737:chemistry / Q000235:genetics*
D003062:Codon; C522806:Crygc protein, human; D038222:gamma-Crystallins