X-linked myotubular myopathy (MTM) is a form of centronuclear myopathy (CNM) associated with mutations in the myotubularin 1 gene. It is found almost always in male infants. It is one of the severest congenital muscle diseases and is characterized by marked muscle weakness, hypotonia and feeding and breathing difficulties.[citation needed]
X-linked myotubular myopathy
Other names
XLMTM
This condition is inherited in an X-linked recessive manner.
This condition is caused by mutations in the myotubularin (MTM1) gene which is located on the long arm of the X chromosome (Xq28). Thus, almost all cases of X-linked MTM occurs in males. Females can be "carriers" for an X-linked genetic abnormality, but usually they will not be clinically affected themselves. Two exceptions for a female with a X-linked recessive abnormality to have clinical symptoms: one is a manifesting carrier and the other is X-inactivation. A manifesting carrier usually has no noticeable problems at birth; symptoms show up later in life. In X-inactivation, the female (who would otherwise be a carrier, without any symptoms), actually presents with full-blown X-linked MTM. Thus, she congenitally presents (is born with) MTM.[1]
Thus, although MTM1 mutations most commonly cause problems in boys, these mutations can also cause clinical myopathy in girls, for the reasons noted above. Girls with myopathy and a muscle biopsy showing a centronuclear pattern should be tested for MTM1 mutations.[1]
Abbreviations XL-MTM, XLMTM or X-MTM are sometimes used to emphasize that the mutation occurs on the X chromosome.
ResearchEdit
Astellas Gene Therapies (earlier called Audentes Therapeutics) is developing an experimental gene therapy to treat the condition. A clinical trial was halted in 2020 after two boys participating in the trial died of liver inflammation and sepsis.[2]
ReferencesEdit
^ abJungbluth H, Sewry C, Buj-Bello A, Kristiansen M, Ørstavik K, Kelsey A, Manzur A, Mercuri E, Wallgren-Pettersson C, Muntoni F (2003). "Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation". Neuromuscul Disord. 13 (1): 55–9. doi:10.1016/S0960-8966(02)00194-3. PMID 12467733. S2CID 11161762.
^Anonymous (2020). "Two boys die in gene therapy trial". Science. 369 (6499): 13.
External linksEdit
GeneReview/NCBI/NIH/UW entry on X-Linked Myotubular Myopathy
August 28, 2023
linked, myotubular, myopathy, form, centronuclear, myopathy, associated, with, mutations, myotubularin, gene, found, almost, always, male, infants, severest, congenital, muscle, diseases, characterized, marked, muscle, weakness, hypotonia, feeding, breathing, . X linked myotubular myopathy MTM is a form of centronuclear myopathy CNM associated with mutations in the myotubularin 1 gene It is found almost always in male infants It is one of the severest congenital muscle diseases and is characterized by marked muscle weakness hypotonia and feeding and breathing difficulties citation needed X linked myotubular myopathyOther namesXLMTMThis condition is inherited in an X linked recessive manner Contents 1 Genetics 2 Research 3 References 4 External linksGenetics EditThis condition is caused by mutations in the myotubularin MTM1 gene which is located on the long arm of the X chromosome Xq28 Thus almost all cases of X linked MTM occurs in males Females can be carriers for an X linked genetic abnormality but usually they will not be clinically affected themselves Two exceptions for a female with a X linked recessive abnormality to have clinical symptoms one is a manifesting carrier and the other is X inactivation A manifesting carrier usually has no noticeable problems at birth symptoms show up later in life In X inactivation the female who would otherwise be a carrier without any symptoms actually presents with full blown X linked MTM Thus she congenitally presents is born with MTM 1 Thus althoughMTM1 mutations most commonly cause problems in boys these mutations can also cause clinical myopathy in girls for the reasons noted above Girls with myopathy and a muscle biopsy showing a centronuclear pattern should be tested for MTM1 mutations 1 Abbreviations XL MTM XLMTM or X MTM are sometimes used to emphasize that the mutation occurs on the X chromosome Research EditAstellas Gene Therapies earlier called Audentes Therapeutics is developing an experimental gene therapy to treat the condition A clinical trial was halted in 2020 after two boys participating in the trial died of liver inflammation and sepsis 2 References Edit a b Jungbluth H Sewry C Buj Bello A Kristiansen M Orstavik K Kelsey A Manzur A Mercuri E Wallgren Pettersson C Muntoni F 2003 Early and severe presentation of X linked myotubular myopathy in a girl with skewed X inactivation Neuromuscul Disord 13 1 55 9 doi 10 1016 S0960 8966 02 00194 3 PMID 12467733 S2CID 11161762 Anonymous 2020 Two boys die in gene therapy trial Science 369 6499 13 External links EditGeneReview NCBI NIH UW entry on X Linked Myotubular Myopathy Retrieved from https en wikipedia org w index php title X linked myotubular myopathy amp oldid 1122569628, wikipedia, wiki, book, books, library,
