X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disorder due 
to mutations in the MTM1 gene. The corresponding protein, myotubularin, contains 
the consensus active site of tyrosine phosphatases (PTP) but otherwise shows no 
homology to other phosphatases. Myotubularin is able to hydrolyze a synthetic 
analogue of tyrosine phosphate, in a reaction inhibited by orthovanadate, and 
was recently shown to act on both phosphotyrosine and phosphoserine. This gene 
is conserved down to yeast and strong homologies were found with human ESTs, 
thus defining a new dual specificity phosphatase (DSP) family. We report the 
presence of novel members of the MTM gene family in Schizosaccharomyces pombe, 
Caenorhabditis elegans, zebrafish, Drosophila, mouse and man. This represents 
the largest family of DSPs described to date. Eight MTM-related genes were found 
in the human genome and we determined the chromosomal localization and 
expression pattern for most of them. A subclass of the myotubularin homologues 
lacks a functional PTP active site. Missense mutations found in XLMTM patients 
affect residues conserved in a Drosophila homologue. Comparison of the various 
genes allowed construction of a phylogenetic tree and reveals conserved residues 
which may be essential for function. These genes may be good candidates for 
other genetic diseases.