PRENATAL-DIAGNOSIS OF X-LINKED MYOTUBULAR MYOPATHY - STRATEGIES USINGNEW AND TIGHTLY LINKED DNA MARKERS

X-linked myotubular myopathy (MTM1) is a severe congenital myopathy ch aracterized by hypotonia, muscle weakness, and associated respiratory insufficiency. Perinatal death is common. The disease locus was shown to be linked to polymorphic markers in Xq28 and we have recently refin ed the MTM1 locus to a physical region of less than one megabase (Mb) at proximal Xq28. Two new microsatellite markers were developed and as signed in the MTM1 candidate region. We applied them and other DNA mar kers for prenatal diagnosis in two families. In one case, an affected fetus was predicted and a recombination event was observed with two mo re distal markers in the region. The second fetus was born unaffected as predicted. The new DNA markers and the precise location of the MTM1 gene provide an improvement for early prenatal diagnosis of the disea se. We present suggestions for different combinations of linked and fl anking DNA markers for maximal informativeness and accuracy.