• mosaic;
  • MTM1;
  • myotubular myopathy;
  • protein tyrosine phosphatases;

X-linked myotubular myopathy (XLMTM; OMIM310400) is a congenital muscle disorder characterized by severe hypotonia and respiratory insufficiency. The disorder was mapped to Xq28 by linkage studies and the MTM1 gene was isolated by positional cloning. The gene product is a 603 amino acid protein named myotubularin. A small domain in its sequence shows high homology to a consensus active site of tyrosine phosphatases, a diverse class of proteins involved in signal transduction, control of cell growth, and differentiation. In this report, two brothers affected with XLMTM are shown to have a point mutation (G1187A) in exon 11 of the MTM1 gene. Surprisingly, their mother does not have this mutation in her lymphocytes. Therefore, she likely has a germline mosaicism. As this is the third report of germline mosaicism in XLMTM, the finding has important implications for genetic counseling.