TY - JOUR
T1 - Novel findings associated with MTM1 suggest a higher number of female symptomatic carriers
AU - Savarese, Marco
AU - Musumeci, Olimpia
AU - Giugliano, Teresa
AU - Rubegni, Anna
AU - Fiorillo, Chiara
AU - Fattori, Fabiana
AU - Torella, Annalaura
AU - Battini, Roberta
AU - Rodolico, Carmelo
AU - Pugliese, Aniello
AU - Piluso, Giulio
AU - Maggi, Lorenzo
AU - D'Amico, Adele
AU - Bruno, Claudio
AU - Bertini, Enrico
AU - Santorelli, Filippo Maria
AU - Mora, Marina
AU - Toscano, Antonio
AU - Minetti, Carlo
AU - Nigro, Vincenzo
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Abnormal genital development
KW - CGH array
KW - MTM1 gene
KW - Next-generation sequencing
KW - X-linked myotubular myopathy
UR - http://www.scopus.com/inward/record.url?scp=84962516913&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962516913&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2016.02.004
DO - 10.1016/j.nmd.2016.02.004
M3 - Article
AN - SCOPUS:84962516913
VL - 26
SP - 292
EP - 299
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
IS - 4-5
ER -