title: X-linked myotubular myopathy due to a complex rearrangement involving a duplication of MTM1 exon 10.
abstract: X-linked myotubular myopathy is a predominantly severe congenital myopathy with central nuclei on muscle biopsy due to mutations in the MTM1 gene encoding myotubularin. We report a boy with typical features of X-linked myotubular myopathy. Sequencing of the MTM1 gene did not reveal any causative mutations. Subsequent MLPA analysis identified a duplication of MTM1 exon 10 both in the patient and his mother. Additional quantitative fluorescent PCR and long-range PCR revealed an additional large deletion (2536bp) within intron 10, 143bp downstream of exon 10, and confirmed the duplication of exon 10. Our findings suggest that complex rearrangements have to be considered in typically affected males with X-linked myotubular myopathy.
authors.affiliation: DNA Laboratory, GSTS Pathology, Guy's Hospital, London, UK. Heinz.Jungbluth@gstt.nhs.uk
authors.forename: N
authors.initials: N
authors.lastname: Trump
authors.forename: T
authors.initials: T
authors.lastname: Cullup
authors.forename: J B G M
authors.initials: JB
authors.lastname: Verheij
authors.forename: A
authors.initials: A
authors.lastname: Manzur
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: S
authors.initials: S
authors.lastname: Abbs
authors.forename: H
authors.initials: H
authors.lastname: Jungbluth
mesh_terms: D041321:Chromosomes, Human, X; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000209:etiology / Q000235:genetics*; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin