Diagnosis of X-linked myotubular myopathy by detection of myotubularin.

Mutations in the MTM1 gene cause X-linked recessive myotubular myopathy (XLMTM; MIM310400). Myotubularin, the implicated protein, is a phosphoinositide phosphatase that belongs to a large protein family conserved through evolution that also includes the antiphosphatase Sbfl and the protein hMTMR2 mutated in Charcot-Marie-Tooth type 4B. Myotubularin is detectable in a variety of cell lines by immunoprecipitation followed by Western blotting. We screened 29 independant patients with XLMTM phenotype and four with centronuclear myopathy. 87% (21/24) of patients with known MTM1 mutations showed abnormal myotubularin levels, including some with missense mutations. Moreover, myotubularin was also undetectable in a patient for whom no mutation could be identified by SSCP screening. The centronuclear cases investigated have a normal level of protein, suggesting that the centronuclear form is not the result of a decrease in myotubularin level. Thus, immunoprecipitation of myotubularin from cultured cells represents a rapid and helpful method for classifying those cases where no mutation was found. On the other hand, the amount of expression may be of diagnostic value for disease course in patients with a mutation.