EXTENSIVE GERMINAL MOSAICISM IN A FAMILY WITH X-LINKED MYOTUBULAR MYOPATHY SIMULATES GENETIC-HETEROGENEITY

A family with two male cousins affected with myotubular myopathy (MTM) was referred to us for genetic counselling. Linkage analysis appeared to exclude the Xq28 region. As a gene for X linked MTM was recently i dentified in Xq28, we screened the obligatory carrier mothers for muta tion. We found a 4 bp deletion in exon 4 of the MTM1 gene, which origi nated from the grandfather of the affected children and which was tran smitted to three daughters. This illustrates the importance of mutatio n detection to avoid pitfalls in linkage analysis that may be caused b y such cases of germinal mosaicism.