X-linked myotubular myopathy (MTM) is a form of

centronuclear myopathy Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in the center of muscle cells instead of their normal location at the periphery. Symptoms of CNM include severe hypotonia, hypoxia-req ...

(CNM) associated with

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s 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.

Genetics

This condition is caused by mutations in the myotubularin (

MTM1 Myotubularin is a protein that in humans is encoded by the ''MTM1'' gene. This gene is a member of a gene family that encodes lipid phosphatases. Myotubularin is required for muscle cell differentiation and mutations in this gene have been ident ...

) gene which is located on the long arm of the

X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

(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 X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into ...

. 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. 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. Abbreviations XL-MTM, XLMTM or X-MTM are sometimes used to emphasize that the mutation occurs on the X chromosome.

Research

Astellas Gene Therapies (earlier called Audentes Therapeutics) is developing an experimental

gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

to treat the condition. A clinical trial was halted in 2020 after two boys participating in the trial died of liver inflammation and sepsis.

References

External links

GeneReview/NCBI/NIH/UW entry on X-Linked Myotubular Myopathy
{{DEFAULTSORT:X-Linked Myotubular Myopathy Myoneural junction and neuromuscular diseases Rare diseases