Germline mosaicism in X-linked myotubular myopathy

X-linked myotubular myopathy (XLMTM; OMIM310400) is a congenital muscle dis order characterized by severe hypotonia and respiratory insufficiency. The disorder was mapped to Xq28 by linkage studies and the MTM1 gene was isolat ed by positional cloning. The gene product is a 603 amino acid protein name d myotubularin. A small domain in its sequence shows high homology to a con sensus active site of tyrosine phosphatases, a diverse class of proteins in volved 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 X LMTM, the finding has important implications for genetic counseling.