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.
Gonzalez-Huerta
Luz M
LM
Department of Genetics, General Hospital of Mexico, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Messina-Baas
Olga M
OM
Cuevas-Covarrubias
Sergio A
SA
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