Gene Summary
RefSeq / NCBIThis gene encodes a dual-specificity phosphatase that acts on both phosphotyrosine and phosphoserine. It is required for muscle cell differentiation and mutations in this gene have been identified as being responsible for X-linked myotubular myopathy. [provided by RefSeq, Jul 2008]
Clinical Phenotype
X-linked myotubular myopathy (XLMTM): severe neonatal hypotonia, respiratory failure requiring ventilation at birth, and ophthalmoplegia. The most severe congenital myopathy; many infants do not survive infancy without respiratory support.
Molecular Mechanism
Myotubularin is a phosphoinositide phosphatase that dephosphorylates PI(3)P, regulating membrane trafficking and autophagy. Loss of MTM1 impairs myofibrillar organization and leads to muscle fibers resembling fetal myotubes (central nuclei with perinuclear myosin clearing).
Clinical Hallmarks & Key Evidence
Muscle biopsy hallmark: large rounded fibers with centrally placed nuclei and a clear 'halo' zone devoid of myofibrils — resembling fetal myotubes, giving the disease its name.
Spiro AJ et al. Arch Neurol. 1966;14(1):1-14.
Aspamotide (resamirigene bilparvovec, AT132), an AAV-delivered MTM1 gene therapy, showed early promise but clinical trials were paused due to unexpected hepatic toxicity in 2021.
Shieh PB et al. N Engl J Med. 2023;389:2294-2306.
Female carriers of MTM1 mutations can develop significant myopathy due to skewed X-inactivation, presenting with weakness and respiratory compromise in adulthood.
Jungbluth H et al. Neuromuscul Disord. 2003;13(1):55-9.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.