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

Objectives: To identify a congenital nystagmus focus on the X chromosome an d to characterize the phenotype of a 4-generation family affected with cong enital nystagmus and color deficiency. Methods: Sixty-five patients underwent an eye-examination, including evalua tion for the presence of nystagmus and color vision abnormalities. Affected patients and obligate carriers of the congenital nystagmus mutation were g enotyped 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, cong enital nystagmus. All examined patients had a visual acuity of 20/60 or bet ter. There were no associated ocular or systemic findings except that 18 of the family members had deficient red-green color vision, which was classif ied as deuteranomaly (the most common form of anomalous trichromacy). Five patients exhibited nystagmus and deuteranomaly. Significant linkage was dem onstrated between the nystagmus phenotype and 11 markers from Xq. The maxim um lod score was 4.84 (theta = 0) and was obtained with marker DXS8041. Ana lysis of recombinants defined the disease interval to lie between markers A TA59C05 and DXS1192 (a 5.4-centimorgan region). The proximity of this locus to the red-green opsin gene cluster(11 centimorgans more telomeric) explai ns the frequent coexistence of nystagmus and color vision deficiency in thi s family. Conclusions: We have identified the genetic locus of the X-linked congenita l nystagmus gene in this family. The critical interval in this report is le ss than half the size of the previously described nystagmus locus. These fi ndings will aid in identifying the gene responsible for this condition.