Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy.

Aldobrando Broccolini, Enzo Ricci, Denise Cassandrini, Carla Gliubizzi, Claudio Bruno, Emmanuel Tonoli, Gabriella Silvestri, Mario Pescatori, Carmelo Rodolico, Stefano Sinicropi, Serenella Servidei, Federico Zara, Carlo Minetti, Pietro A. Tonali, Massimiliano Mirabella

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)632
Number of pages1
JournalHuman Mutation
Volume23
Issue number6
Publication statusPublished - Jun 2004

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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