Clinical characterization and linkage analysis of a family with congenital X-linked nystagmus and deuteranomaly

Abstract

Objectives: To identify a congenital nystagmus locus on the X chromosome and to characterize the phenotype of a 4-generation family affected with congenital nystagmus and color deficiency.

Methods: Sixty-five patients underwent an eye examination, including evaluation for the presence of nystagmus and color vision abnormalities. Affected patients and obligate carriers of the congenital nystagmus mutation were genotyped with short tandem repeat polymorphisms located on the X chromosome, and these data were subjected to linkage analysis.

Results: Fourteen patients were affected with a horizontal, conjugate, congenital nystagmus. All examined patients had a visual acuity of 20/60 or better. There were no associated ocular or systemic findings except that 18 of the family members had deficient red-green color vision, which was classified as deuteranomaly (the most common form of anomalous trichromacy). Five patients exhibited nystagmus and deuteranomaly. Significant linkage was demonstrated between the nystagmus phenotype and 11 markers from Xq. The maximum lod score was 4.84 (theta = 0) and was obtained with marker DXS8041. Analysis of recombinants defined the disease interval to lie between markers ATA59C05 and DXS1192 (a 5.4-centimorgan region). The proximity of this locus to the red-green opsin gene cluster (11 centimorgans more telomeric) explains the frequent coexistence of nystagmus and color vision deficiency in this family.

Conclusions: We have identified the genetic locus of the X-linked congenital nystagmus gene in this family. The critical interval in this report is less than half the size of the previously described nystagmus locus. These findings will aid in identifying the gene responsible for this condition.