title: Necklace fibers as histopathological marker in a patient with severe form of X-linked myotubular myopathy.
abstract: X-linked myotubular myopathy due to mutations in the MTM1 gene is classically characterized by a severe neonatal phenotype and a typical muscle biopsy presenting globular and centrally located nuclei in muscle myofibers. Recently, four patients with mild late-onset form have been described, a male with a hemizygous mutation and three females with heterozygous mutations in the MTM1 gene. The muscle biopsies were performed at 13-35 years of age and a new histological marker, the necklace fibers, was described. Here, we report two siblings with the pathogenic c.664 C>T mutation in the MTM1 gene, presenting a severe muscle weakness and respiratory impairment requiring ventilatory support since the first months of life until death, at the age of 36 months and 5 months. In the older brother the muscle biopsy, performed at the age of 30 months, showed almost 100% of necklace fibers, which were not present in the younger one submitted to muscle biopsy at 5 months of age. Our findings confirm the necklace fibers can be a histopathological finding of MTM1 myopathies, even in the severe neonatal form, and suggest that the necklace fibers appear or increase in number over time.
authors.affiliation: Department of Pediatrics, Medical School of Federal University of Minas Gerais, Brazil. gurgelju@yahoo.com.br
authors.forename: Juliana
authors.initials: J
authors.lastname: Gurgel-Giannetti
authors.forename: Edmar
authors.initials: E
authors.lastname: Zanoteli
authors.forename: Eralda Luiza
authors.initials: EL
authors.lastname: de Castro Concentino
authors.forename: Osorio
authors.initials: O
authors.lastname: Abath Neto
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
authors.forename: Umbertina Conti
authors.initials: UC
authors.lastname: Reed
authors.forename: Mariz
authors.initials: M
authors.lastname: Vainzof
mesh_terms: D002675:Child, Preschool; D017809:Fatal Outcome; D006801:Humans; D007223:Infant; D008297:Male; D018908:Muscle Weakness / Q000235:genetics / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D020914:Myopathies, Structural, Congenital / Q000235:genetics / Q000473:pathology*; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*; D035781:Siblings
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin