Prenatal diagnosis of X-linked centronuclear myopathy by linkage analysis

The X-linked recessive centronuclear/myotubular myopathy (XLR-CNM/MTM1), a severe neonatal disorder characterized by generalized hypotonia, muscle weakness, and primary asphyxia, has recently been mapped to Xq28. This report presents the first four prenatal diagnoses of XLR-CNM using DNA markers of the Xq28 region. The analyses of one female and three male fetuses revealed maternal transmission of the XLR-CNM-associated alleles in all four cases. Two of the male fetuses have been aborted, and the pregnancies of the third male and the female fetuses have been continued. The diagnosis of XLR-CNM at the birth of the third boy, as well as the pathologic findings in the muscle of one of the aborted fetuses, confirmed the linkage results of the prenatal analyses. Our findings prove the DNA markers St14, cpX67, DX13, and pSt35-691 to be useful in prenatal diagnosis of XLR-CNM and present the possibility to confirm the diagnosis by histologic examination of the first-trimester abortus. This permits an indirect prenatal diagnosis of XLR-CNM in chorionic villus biopsies at 9 to 12 wk gestation, using DNA-based linkage analyses allowing early termination of an affected pregnancy.