title: Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H.
abstract: In 2005 the commonality of sarcotubular myopathy (STM) and limb girdle muscular dystrophy type 2H (LGMD2H) was demonstrated, as both are caused by the p D487N missense mutation in TRIM32 originally found in the Manitoba Hutterite population. Recently, three novel homozygous TRIM32 mutations have been described in LGMD patients. Here we describe a three generation Swedish family clinically presenting with limb girdle muscular weakness and histological features of a microvacuolar myopathy. The two index patients were compound heterozygotes for a frameshift mutation in TRIM32 (c.1560delC ) and a 30 kb intragenic deletion, encompassing parts of intron 1 and the entire exon 2 of TRIM32. In these patients, no full-length or truncated TRIM32 could be detected. Interestingly, heterozygous family members carrying only one mutation showed mild clinical symptoms and vacuolar changes in muscle. In our family, the phenotype encompasses additionally a mild demyelinating polyneuropathic syndrome. Thus STM and LGMD2H are the result of loss of function mutations that can be either deletions or missense mutations.
authors.affiliation: Departments of Clinical Sciences and Neurology Karolinska Institutet Danderyds Hospital, Division of Rehabilitation Medicine, Stockholm, Sweden.
authors.forename: Kristian
authors.initials: K
authors.lastname: Borg
authors.forename: Rolf
authors.initials: R
authors.lastname: Stucka
authors.forename: Matthew
authors.initials: M
authors.lastname: Locke
authors.forename: Eva
authors.initials: E
authors.lastname: Melin
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Ahlberg
authors.forename: Ursula
authors.initials: U
authors.lastname: Klutzny
authors.forename: Maja von der
authors.initials: Mv
authors.lastname: Hagen
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Klaus
authors.initials: K
authors.lastname: Wrogemann
authors.forename: Lars-Eric
authors.initials: LE
authors.lastname: Thornell
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Blake
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D013548:Sweden; D014157:Transcription Factors / Q000235:genetics*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases