A GENE MUTATED IN X-LINKED MYOTUBULAR MYOPATHY DEFINES A NEW PUTATIVETYROSINE PHOSPHATASE FAMILY CONSERVED IN YEAST

X-linked recessive myotubular myopathy (MTM1) is characterized by seve re hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. We have restricted the candidate region to 280 kb a nd characterized two candidate genes using positional cloning strategi es. The presence of frameshift or missense mutations (of which two are new mutations) in seven patients proved that one of these genes is in deed implicated in MTM1. The protein encoded by the MTM1 gene is highl y conserved in yeast, which is surprising for a muscle specific diseas e. The protein contains the consensus sequence for the active site of tyrosine phosphatases, a wide class of proteins involved in signal tra nsduction. At least three other genes, one located within 100 kb dista l from the MTM1 gene, encode proteins with very high sequence similari ties and define, together with the MTM1 gene, a new family of putative tyrosine phosphatases in man.