Genomic organization of a 225-kb region in Xq28 containing the gene for X-linked myotubular myopathy (MTM1) and a related gene (MTMR1)

Citation
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
Citations number
50
Categorie Soggetti
Molecular Biology & Genetics
Journal title
GENOMICS
ISSN journal
08887543 → ACNP
Volume
54
Issue
2
Year of publication
1998
Pages
256 - 266
Database
ISI
SICI code
0888-7543(199812)54:2<256:GOOA2R>2.0.ZU;2-1
Abstract
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.