Deafness in blue-eyed white cats: the uphill road to solving polygenic disorders.

The pure white cat with luminous blue eyes is an attractive image familiar to many. These animals are well-known to be commonly affected by a congenital hereditary deafness that may affect one or both ears; the deafness is linked to the so-called W gene. Reports of this condition date back to at least the 1930s (Bamber, 1933), and many investigators have studied it in subsequent years (Wolff, 1942; Wilson and Kane, 1959; Bosher and Hallpike, 1965; Bergsma and Brown, 1971; Mair, 1973; Mair and Elverland, 1977; Pujol et al., 1977; Rebillard et al., 1981a,b; Saada et al., 1996; Ryugo et al., 1998, 2003). The white (W) pigment gene in cats is autosomal dominant over colour, and is unrelated to albinism (Little, 1957; Searle, 1968). Cats carrying the W gene are not always solid white, often having coloured spots on their heads that may fade or disappear with age. Unlike dogs homozygous with the dominant merle pigmentation gene, homozygous white cats do not typically have visual or reproductive defects, but they are prone to the occurrence of blue irises (one or both) and deafness (either unilateral or bilateral), and the deafness likelihood increases with the number of blue eyes (Delack, 1984). Whether the cat is heterozygous or homozygous for W, the blue eyes and deafness have incomplete penetrance. It has been suggested that longhaired cats have a higher prevalence of blue eyes and deafness than short-haired cats (Mair, 1973), but this has not been confirmed. Cats instead carrying the underlying c Siamese dilution pigment gene can have blue eyes without deafness, and it has been suggested that the presence of this gene explains why purebred white cats are less often deaf than mixed-breed white cats (Pedersen, 1991), but no studies have documented this assertion about prevalence. The white gene is present in many cat breeds, but unfortunately no data have been available on relative rates of occurrence of deafness among them (see below). A dominant piebald gene (S), also known as white spotting, is also found in various cat breeds (Pedersen, 1991; Searle, 1968), but there has been no report of deafness associated with its presence. Delack (1984) analyzed three studies of deafness in nonpure breed white cats that included a total of 256 cats