| FRAGILE X MENTAL RETARDATION SYNDROME |
| CYTOGENETICS: Lubs (1969) first described a marker X chromosome in mentally retarded males; a secondary constriction on the distal long arm gave the appearance of large satellites. Lubs (1969) suggested that either the anomalous region itself or a closely linked recessive gene might account for X-linked retardation. This observation went unconfirmed for years until cytogeneticists reverted to a folate-deficient medium for tissue culture such as Lubs (1969) employed. Appearance of this secondary constriction (widely referred to as a fragile site) was shown to be dependent on folate deficiency in the culture medium (which leads to deficiency of thymidine monophosphate), localized to the interface between Xq27 and q28, and associated with mental retardation and macroorchidism in males (Giraud et al., 1976; Harvey et al., 1977; Sutherland, 1977). Sutherland was in Melbourne when he made his initial observations on the fragile X. When he went to Adelaide, he upgraded his laboratory, changing from 199 to F10 culture medium to give better chromosomes for banding. The failure to find the fragile X with the new medium led to his discovery of the critical role of folate (Gerald, 1983). Turner et al. (1978) suggested labeling the marker secondary constriction Xq27; however, convention requires that 'a break suspected at an interface between two bands is identified arbitrarily by the higher of the two band numbers' (ISCN, 1978; section 2.4.4.2). Brookwell and Turner (1983) again concluded that the fragile site is in band Xq27, close to the 27-28 interface. The marker X is not preferentially inactivated in heterozygotes (Lubs, 1969; Martin et al., 1980) |
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