Prenatal diagnosis of X-linked myotubular myopathy: strategies using new and tightly linked DNA markers.

X-linked myotubular myopathy (MTM1) is a severe congenital myopathy characterized 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 refined the MTM1 locus to a physical region of less than one megabase (Mb) at proximal Xq28. Two new microsatellite markers were developed and assigned in the MTM1 candidate region. We applied them and other DNA markers for prenatal diagnosis in two families. In one case, an affected fetus was predicted and a recombination event was observed with two more 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 disease. We present suggestions for different combinations of linked and flanking DNA markers for maximal informativeness and accuracy.