Novel findings associated with MTM1 suggest a higher number of female symptomatic carriers

Marco Savarese, Olimpia Musumeci, Teresa Giugliano, Anna Rubegni, Chiara Fiorillo, Fabiana Fattori, Annalaura Torella, Roberta Battini, Carmelo Rodolico, Aniello Pugliese, Giulio Piluso, Lorenzo Maggi, Adele D'Amico, Claudio Bruno, Enrico Bertini, Filippo Maria Santorelli, Marina Mora, Antonio Toscano, Carlo Minetti, Vincenzo Nigro

Research output: Contribution to journalArticlepeer-review


Mutations in the MTM1 gene cause X-linked myotubular myopathy (XLMTM), characterized by neonatal hypotonia and respiratory failure, and are responsible for a premature mortality in affected males. Female carriers are usually asymptomatic but they may present with muscular weakness because of a hypothesized skewed pattern of X-chromosome inactivation.By combining next generation sequencing (NGS) and CGH array approaches, we have investigated the role of MTM1 variants in a large cohort of undiagnosed patients with a wide spectrum of myopathies. Seven novel XLMTM patients have been identified, including two girls with an unremarkable family history for myotubular myopathy.Moreover, we have detected and finely mapped a large deletion causing a myotubular myopathy with abnormal genital development.Our data confirm that the severe neonatal onset of the disease in male infants is sufficient to address the direct molecular testing toward the MTM1 gene and, above all, suggest that the number of undiagnosed symptomatic female carriers is probably underestimated.

Original languageEnglish
Pages (from-to)292-299
Number of pages8
JournalNeuromuscular Disorders
Issue number4-5
Publication statusPublished - Apr 1 2016


  • Abnormal genital development
  • CGH array
  • MTM1 gene
  • Next-generation sequencing
  • X-linked myotubular myopathy

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology


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