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 journalArticle

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

Fingerprint

Mutation
Genes
Missense Mutation
Bahamas
Chromosomes, Human, Pair 13
Atrophy
Lower Extremity
Exons
Nucleotides
Nonaka type Distal myopathy
Inclusion body myopathy autosomal recessive
Muscles

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Broccolini, A., Ricci, E., Cassandrini, D., Gliubizzi, C., Bruno, C., Tonoli, E., ... Mirabella, M. (2004). Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy. Human Mutation, 23(6), 632.

Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy. / Broccolini, Aldobrando; Ricci, Enzo; Cassandrini, Denise; Gliubizzi, Carla; Bruno, Claudio; Tonoli, Emmanuel; Silvestri, Gabriella; Pescatori, Mario; Rodolico, Carmelo; Sinicropi, Stefano; Servidei, Serenella; Zara, Federico; Minetti, Carlo; Tonali, Pietro A.; Mirabella, Massimiliano.

In: Human Mutation, Vol. 23, No. 6, 06.2004, p. 632.

Research output: Contribution to journalArticle

Broccolini, A, Ricci, E, Cassandrini, D, Gliubizzi, C, Bruno, C, Tonoli, E, Silvestri, G, Pescatori, M, Rodolico, C, Sinicropi, S, Servidei, S, Zara, F, Minetti, C, Tonali, PA & Mirabella, M 2004, 'Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy.', Human Mutation, vol. 23, no. 6, pp. 632.
Broccolini, Aldobrando ; Ricci, Enzo ; Cassandrini, Denise ; Gliubizzi, Carla ; Bruno, Claudio ; Tonoli, Emmanuel ; Silvestri, Gabriella ; Pescatori, Mario ; Rodolico, Carmelo ; Sinicropi, Stefano ; Servidei, Serenella ; Zara, Federico ; Minetti, Carlo ; Tonali, Pietro A. ; Mirabella, Massimiliano. / Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy. In: Human Mutation. 2004 ; Vol. 23, No. 6. pp. 632.
@article{aa6b3bf7c03d4a83a3eaf22b0fc8d3fc,
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.",
author = "Aldobrando Broccolini and Enzo Ricci and Denise Cassandrini and Carla Gliubizzi and Claudio Bruno and Emmanuel Tonoli and Gabriella Silvestri and Mario Pescatori and Carmelo Rodolico and Stefano Sinicropi and Serenella Servidei and Federico Zara and Carlo Minetti and Tonali, {Pietro A.} and Massimiliano Mirabella",
year = "2004",
month = "6",
language = "English",
volume = "23",
pages = "632",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Novel GNE mutations in Italian families with autosomal recessive hereditary inclusion-body myopathy.

AU - Broccolini, Aldobrando

AU - Ricci, Enzo

AU - Cassandrini, Denise

AU - Gliubizzi, Carla

AU - Bruno, Claudio

AU - Tonoli, Emmanuel

AU - Silvestri, Gabriella

AU - Pescatori, Mario

AU - Rodolico, Carmelo

AU - Sinicropi, Stefano

AU - Servidei, Serenella

AU - Zara, Federico

AU - Minetti, Carlo

AU - Tonali, Pietro A.

AU - Mirabella, Massimiliano

PY - 2004/6

Y1 - 2004/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=4544304099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544304099&partnerID=8YFLogxK

M3 - Article

C2 - 15146476

AN - SCOPUS:4544304099

VL - 23

SP - 632

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 6

ER -