title: Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy.
abstract: The most common form of autosomal recessive (AR) hereditary inclusion-body myopathy (HIBM), originally described in Persian-Jewish families, is characterized by onset in early adult life with weakness and atrophy of distal lower limb muscles, which progress proximally and relatively spare the quadriceps. AR HIBM is associated with mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE) on chromosome 9p12-13. In the present study we have identified seven novel GNE mutations in patients from five unrelated Italian families with clinical and pathologic features indicative of AR HIBM. Four were missense mutations (c.1556A>G [p.N519S], c.79C>T [p.P27S], c.1798G>A [p.A600T] and c.616G>A [p.G206S]), two consisted in a single-base deletion (c.616delG [p.G206fsX4] and c.1130delT [p.I377fsX16]) and one in an intronic single-base insertion (c.1070+2dupT). These latter findings further extend the type of GNE mutations associated with HIBM. Furthermore, in one patient we also identified the c.737G>A [p.R246Q] missense mutation that corresponds to the one previously reported in a family from the Bahamas. Interestingly, in two of our families distinct mutations affected nucleotide c.616 in exon 3 (c.616delG and c.616G>A). The possibility of specific portions of the gene being more prone to mutations remains to be elucidated.
authors.affiliation: Department of Neuroscience, Catholic University, Rome, Italy. a.broccolini@rm.unicatt.it
authors.forename: Aldobrando
authors.initials: A
authors.lastname: Broccolini
authors.forename: Enzo
authors.initials: E
authors.lastname: Ricci
authors.forename: Denise
authors.initials: D
authors.lastname: Cassandrini
authors.forename: Carla
authors.initials: C
authors.lastname: Gliubizzi
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tonoli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Silvestri
authors.forename: Mario
authors.initials: M
authors.lastname: Pescatori
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rodolico
authors.forename: Stefano
authors.initials: S
authors.lastname: Sinicropi
authors.forename: Serenella
authors.initials: S
authors.lastname: Servidei
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Pietro A
authors.initials: PA
authors.lastname: Tonali
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mirabella
mesh_terms: D004252:DNA Mutational Analysis; D005808:Genes, Recessive; D006801:Humans; D007558:Italy; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000201:enzymology / Q000235:genetics*
chemical_list: D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase