RELATIONSHIP BETWEEN CHARCOT-MARIE-TOOTH-1A AND SMITH-MAGENIS REGIONS- SNU3 MAY BE A CANDIDATE GENE FOR THE SMITH-MAGENIS SYNDROME

The juxtacentromeric region of the human chromosome 17 short arm (17p1 1.2-p12) contains genes involved in the Charcot - Marie - Tooth type 1 A disease (CMT1A) and the Smith - Magenis syndrome (SMS). CMT1A is ass ociated with a duplication of a short segment whereas SMS is linked to microdeletions, extending toward the centromere. We describe the cons truction and analysis of a 5 Mb YAC contig spanning the CMT1 A duplica ted segment and the distal part of four SMS microdeletions. We conclud ed that the YAC contig contains about 1Mb of genomic DNA which is dele ted in the four SMS patients analysed. Moreover two YACs contain both STS deleted in SMS (U3) and STS duplicated in CMT1A (5H5), but the pro ximal breakpoint associated with the CMT1A duplication is not the same as the distal SMS breakpoint we studied. Finally we located five new STS in SMS deletion. Two of them, a microsatellite (D17S805(23)) and t he gene coding for small nuclear RNA U3, have been localized in the co ntig we described. We may also note that snU3 is the first expressed s equence localized in an SMS deletion so far. The possible participatio n of this gene in the SMS phenotype is discussed.