title: Clinical and genetic heterogeneity in chromosome 9p associated hereditary inclusion body myopathy: exclusion of GNE and three other candidate genes.
abstract: We have previously reported a new autosomal dominant inclusion body myopathy clinically resembling limb girdle muscular dystrophy, associated with Paget disease of bone in the majority and frontotemporal dementia in a third of individuals. The critical locus for this unique disorder now termed IBMPFD is 9 p21.1-p12, spans 5.5 Mb and contains the gene responsible for the recessive quadriceps-sparing inclusion body myopathy (IBM2). Mutation analysis of the GNE gene associated with IBM2 in affected individuals from four IBMPFD families did not identify any mutations, indicating that the two disorders are not allelic. Expression studies indicate that GNE has a tissue-specific splice pattern, with four splice variants. Mutation analysis in three other candidate genes (beta-tropomyosin, NDUFB6 and SMU1) did not identify any mutations.
authors.affiliation: Division of Genetics and Metabolism, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Fegan 5, Boston, MA 02115, USA.
authors.forename: Giles D J
authors.initials: GD
authors.lastname: Watts
authors.forename: M
authors.initials: M
authors.lastname: Thorne
authors.forename: M J
authors.initials: MJ
authors.lastname: Kovach
authors.forename: A
authors.initials: A
authors.lastname: Pestronk
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Kimonis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D002238:Carbohydrate Epimerases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D004252:DNA Mutational Analysis / Q000379:methods; D004274:DNA, Recombinant; D003704:Dementia / Q000150:complications / Q000235:genetics; D005091:Exons; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000150:complications / Q000235:genetics; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000150:complications / Q000235:genetics*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010001:Osteitis Deformans / Q000150:complications / Q000235:genetics; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014335:Tropomyosin / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004274:DNA, Recombinant; D005819:Genetic Markers; D009687:Nuclear Proteins; D012333:RNA, Messenger; C432686:Smu-1 protein, C elegans; D014335:Tropomyosin; D009247:NADH, NADPH Oxidoreductases; D017853:Phosphotransferases (Alcohol Group Acceptor); C018765:N-acylmannosamine kinase; D002238:Carbohydrate Epimerases; C024519:N-acyl-D-glucosamine 2-epimerase; C498259:RENBP protein, human