CSNB is a recessive nondegenerative disease that can manifest in one of two forms, complete and incomplete, each of which results from the mutations of a different gene. Several mutations in the CACNA1F gene, also identified by Bech-Hansen and colleagues, were found to cause the less severe, or incomplete, form of CSNB (Nat. Genet. 1998, 19, 264–267). By contrast, the more debilitating, or complete, form of CSNB is the result of NYX mutations. Patients with complete CSNB show impaired retinal rod function and more severe myopia than patients with the incomplete variety.

The scientists studied 22 families in which affected males had been diagnosed with complete X-linked CSNB. In each of the families, a mutated version of NYX was present. A total of 14 different mutations were observed, including one “founder” mutation in seven families in the United States.

NYX encodes a glycosylphosphatidyl-anchored protein called nyctalopin, a unique member of the small leucine-rich proteoglycan family of extracellular matrix proteins. This protein plays an important role in the development of the neural pathways within the retina, potentially functioning as an adhesion molecule in the formation of neuronal synapses. NYX mutations subsequently lead to errors in nyctalopin that hinder its role in making retinal nerve cell connections. Significant mutations disrupt the retinal processes that are normally stimulated by darkness or dim light.

With the discovery of NYX, a detailed study of the pathogenesis in complete CSNB can now be carried out. This next step will be essential for the long-term goal of developing treatments and finding a cure.