X-LINKED MYOTUBULAR MYOPATHY (MTM1) MAPS BETWEEN DXS304 AND DXS305, CLOSELY LINKED TO THE DXS455 VNTR AND A NEW, HIGHLY INFORMATIVE MICROSATELLITE MARKER (DXS1684)

The locus for X Linked recessive myotubular myopathy (MTM1) has previo usly been mapped to Xq28 by linkage analysis. We report two new famili es that show recombination between MTM1 and either DXS304 or DXS52. Th ese families and a third previously described recombinant family were analysed with two highly polymorphic markers in the DXS303-DXS52 inter val, the DXS455 VNTR and a newly characterised microsatellite, DXS1684 (82% heterozygosity). These markers did not recombine with MTM1 in th e three families. Together with the recent mapping of an interstitial X chromosome deletion in a female patient with moderate signs of myotu bular myopathy, our data suggest the following order of loci in Xq28: cen-DXS304-(DXS455, MTM1)-DXS1684-DXS305-DXS52-tel. This considerably refined localisation of the MTM1 locus should facilitate positional cl oning of the gene. The availability of highly polymorphic and very clo sely linked markers will markedly improve carrier and prenatal diagnos is of MTM1.