New phenotype associated with an Arg116Cys mutation in the CRYAA gene: nuclear cataract, iris coloboma, and microphthalmia.

Objective: To describe a new phenotype with an arginine-to-cysteine mutation at position 116 (Arg116Cys) in the CRYAA gene.

Methods: We investigated a 4-generation French family with autosomal dominant cataract and performed a genetic linkage analysis using microsatellite DNA markers encompassing 15 known cataract loci. Exons 1, 2, and 3 and flanking intronic sequences of the CRYAA gene were amplified and analyzed using direct sequencing.

Results: All of the affected individuals had nuclear cataract and iris coloboma. Genetic analysis revealed the previously described Arg116Cys mutation in the CRYAA gene in the heterozygous state in all of the affected members of the family but not in unaffected individuals.

Conclusion: To our knowledge, this is the first case to date in which an Arg116Cys mutation in the CRYAA gene was associated with nuclear cataract and iris coloboma.

Clinical Relevance: This study indicates that an Arg116Cys mutation in the CRYAA gene could be associated with an unusual phenotype in affected individuals. In this family, the clinical observation of iris coloboma allows for the possibility of identifying individuals carrying the mutation. Iris coloboma is particularly important in terms of perinatal diagnosis because its detection in the newborn requires a careful and regular examination of the lens.