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

doi:10.1016/j.nmd.2016.02.004

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

Fondazione Stella Maris

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English
Pages (from-to)	292-299
Number of pages	8
Journal	Neuromuscular Disorders
Volume	26
Issue number	4-5
DOIs	https://doi.org/10.1016/j.nmd.2016.02.004
Publication status	Published - Apr 1 2016

Keywords

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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10.1016/j.nmd.2016.02.004

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Savarese, M., Musumeci, O., Giugliano, T., Rubegni, A., Fiorillo, C., Fattori, F., Torella, A., Battini, R., Rodolico, C., Pugliese, A., Piluso, G., Maggi, L., D'Amico, A., Bruno, C., Bertini, E., Santorelli, F. M., Mora, M., Toscano, A., Minetti, C., & Nigro, V. (2016). Novel findings associated with MTM1 suggest a higher number of female symptomatic carriers. Neuromuscular Disorders, 26(4-5), 292-299. https://doi.org/10.1016/j.nmd.2016.02.004

Novel findings associated with MTM1 suggest a higher number of female symptomatic carriers. / Savarese, Marco; Musumeci, Olimpia; Giugliano, Teresa; Rubegni, Anna ; Fiorillo, Chiara; Fattori, Fabiana; Torella, Annalaura; Battini, Roberta; Rodolico, Carmelo; Pugliese, Aniello; Piluso, Giulio; Maggi, Lorenzo; D'Amico, Adele; Bruno, Claudio; Bertini, Enrico; Santorelli, Filippo Maria; Mora, Marina; Toscano, Antonio; Minetti, Carlo; Nigro, Vincenzo.

In: Neuromuscular Disorders, Vol. 26, No. 4-5, 01.04.2016, p. 292-299.

Research output: Contribution to journal › Article › peer-review

Savarese, M, Musumeci, O, Giugliano, T, Rubegni, A , Fiorillo, C, Fattori, F, Torella, A, Battini, R, Rodolico, C, Pugliese, A, Piluso, G, Maggi, L, D'Amico, A, Bruno, C, Bertini, E, Santorelli, FM, Mora, M, Toscano, A, Minetti, C & Nigro, V 2016, 'Novel findings associated with MTM1 suggest a higher number of female symptomatic carriers', Neuromuscular Disorders, vol. 26, no. 4-5, pp. 292-299. https://doi.org/10.1016/j.nmd.2016.02.004

Savarese, Marco ; Musumeci, Olimpia ; Giugliano, Teresa ; Rubegni, Anna ; Fiorillo, Chiara ; Fattori, Fabiana ; Torella, Annalaura ; Battini, Roberta ; Rodolico, Carmelo ; Pugliese, Aniello ; Piluso, Giulio ; Maggi, Lorenzo ; D'Amico, Adele ; Bruno, Claudio ; Bertini, Enrico ; Santorelli, Filippo Maria ; Mora, Marina ; Toscano, Antonio ; Minetti, Carlo ; Nigro, Vincenzo. / Novel findings associated with MTM1 suggest a higher number of female symptomatic carriers. In: Neuromuscular Disorders. 2016 ; Vol. 26, No. 4-5. pp. 292-299.

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abstract = "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.",

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AU - Bertini, Enrico

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

Abstract

Keywords

ASJC Scopus subject areas

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