P. Kioschis et al., Genomic organization of a 225-kb region in Xq28 containing the gene for X-linked myotubular myopathy (MTM1) and a related gene (MTMR1), GENOMICS, 54(2), 1998, pp. 256-266
MTM1 is responsible for X-linked recessive myotubular myopathy, which is a
congenital muscle disorder linked to Xq28. MTM1 is highly conserved from ye
ast to humans. A number of related genes also exist. The MTM1 gene family c
ontains a consensus sequence consisting of the active enzyme site of protei
n tyrosine phosphatases (PTPs), suggesting that they belong to a new family
of PTPs. Database searches revealed homology of myotubularin and all relat
ed peptides to the cisplatin resistance-associated alpha protein, which imp
licates an as yet unknown function. In addition, homology to the Sbf1 prote
in (SET binding factor 1), involved in the oncogenic transformation of fibr
oblasts and differentiation of myoblasts, was also evident. We describe 225
kb of genomic sequence containing MTM1 and the related gene, MTMR1, which
lies 20 kb distal to MTM1. Although there is only moderate conservation of
the exons, the striking similarity in the gene structures indicates that th
ese two genes arose by duplication. calculations suggest that this event oc
curred early in evolution long before separation of the human and mouse lin
eages. So far, mutations have been identified in the coding sequence of onl
y 65% of the patients analyzed, indicating that the remaining mutations may
lie in noncoding regions of MTM1 or possibly in MTMR1. Knowledge of the ge
nomic sequence will facilitate mutation analyses of the coding and noncodin
g sequences of MTM1 and MTMR1. (C) Academic Press.