CHROMOSOME MAPPING OF RETT-SYNDROME - A LIKELY CANDIDATE REGION ON THE TELOMERE OF XQ

Rett syndrome (RS) is a disease of neurological development. First rep orted 30 years ago in 1966, its biological and genetic basis remains o bscure. RS is commonly thought of as an X linked dominant disorder let hal to hemizygous males. The few familial cases would arise through mo saicism or because of occasional females failing to manifest the disor der through skewed X inactivation in relevant cell types. We have one family where the mother and daughter are affected with RS, and which c an be explained according to this hypothesis. If the alternative propo sal of Thomas (1996) is correct, that the lack of males affected by su ch disorders is the result of a high male to female ratio of germline mutations rather than of gestational lethality, then the RS gene shoul d be located on the grandpaternal chromosome. Genomic screening with m arkers covering the whole X chromosome has been performed. Studies usi ng multiple informative markers indicate that the RS locus is Likely t o be located close to one of the X chromosome telomeres. Further inves tigations in eight additional families suggest the most likely region for the RS gene to be is the distal part of Xq (Xq28).