Distal myopathy caused by homozygous missense mutations in the nebulin gene

Carina Wallgren-Pettersson; Vilma-Lotta Lehtokari; Hannu Kalimo; Anders Paetau; Elina Nuutinen; Peter Hackman; Caroline Sewry; Katarina Pelin; Bjarne Udd
June 2007
Brain: A Journal of Neurology;Jun2007, Vol. 130 Issue 6, p1465
Academic Journal
We describe a novel, recessively inherited distal myopathy caused by homozygous missense mutations in the nebulin gene (NEB), in which other combinations of mutations are known to cause nemaline (rod) myopathy (NM). Two different missense mutations were identified in homozygous form in seven Finnish patients from four unrelated families with childhood or adult-onset foot drop. Both mutations, when combined in compound heterozygous form with more disruptive mutations in NEB, are known to cause NM. Hitherto, no patients with NM have been found to have two missense mutations in NEB. Muscle weakness predominantly affected ankle dorsiflexors, finger extensors and neck flexors, a distribution different both from the patterns of weakness seen in NM caused by NEB mutations, and those of the known recessively inherited distal myopathies. Singleton cases need to be distinguished from the Laing type of distal myopathy. Histologically, this myopathy differs from NM in that nemaline bodies were not detectable with routine light microscopy, and they were inconspicuous or absent even with electron microscopy. Rimmed vacuoles, commonly seen in other distal myopathies, were not a feature. We conclude that homozygous missense mutations in NEB cause a novel distal myopathy, predominantly involving lower leg extensor muscles, finger extensors and neck flexors.


Related Articles

  • Missense mutations of ACTA1 cause dominant congenital myopathy with cores. Kaindl, A. M.; Rüschendorf, F.; Krause, S.; Goebel, H.-H.; Koehler, K.; Becker, C.; Pongratz, D.; Müller-Höcker, J.; Nürnberg, P.; Stoltenburg-Didinger, G.; Lochmüller, H.; Huebner, A. // Journal of Medical Genetics;Nov2004, Vol. 41 Issue 11, p842 

    Cites a study which identified mutations of ACTA1 as a cause of autosomal dominant core myopathy in two families of different ethnic origin. Ability of ACTA1 to cause three forms of congenital myopathy; Mutations of the skeletal muscle alpha-actin gene; Manifestation of mild and non-progressive...

  • Reply to Brodehl et al. Hedberg, Carola; Melberg, Atle; Kuhl, Angelika; Jenne, Dieter; Oldfors, Anders // European Journal of Human Genetics;Jun2013, Vol. 21 Issue 6, p590 

    A response from the authors of the article "Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation," which discusses desmine gene (DES) mutation, is presented.

  • REVIEW The restriction site mutation (RSM) method: clinical applications. G.J.S. Jenkins // Mutagenesis;Jan2004, Vol. 19 Issue 1, p3 

    The restriction site mutation (RSM) method has been developed over the past 13 years as a sensitive mutation test which can detect mutations in restriction sites in any gene. Due to the fact that 5/8 of the main mutation hotspots in the TP53 gene fall within restriction sites, RSM can analyse...

  • THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression. Cheng, Fu; Ozelius, Laurie; Wan, Xin; Feng, Jia; Ma, Ling; Yang, Ying; Wang, Lin // Journal of Neurology;Feb2012, Vol. 259 Issue 2, p342 

    Mutations in the THAP1 gene were recently identified as the cause of DYT6 primary dystonia. More than 40 mutations in this gene have been described in different populations. However, no previous report has identified sequence variations that affect the transcript process of the THAP1 gene. In...

  • A novel missense mutation in the GNE gene in an Iranian patient with hereditary inclusion body myopathy. Behnam, Mahdiyeh; Shin Jin-Hong; Dae-Seong Kim; Basiri, Keivan; Nilipour, Yalda; Sedghi, Maryam // Journal of Research in Medical Sciences;Aug2014, Vol. 19 Issue 8, p792 

    Hereditary inclusion body myopathy (hIBM) is an adult-onset hereditary myopathy, usually with distal onset and quadriceps sparing. This myopathy is autosomal recessive and associated to UPD-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene mutations. In this study, we...

  • Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy. Furihata, Tomomi; Satoh, Naoki; Ohishi, Tomoharu; Ugajin, Miyuki; Kameyama, Yoshio; Morimoto, Kaori; Matsumoto, Sayaka; Yamashita, Keiko; Kobayashi, Kaoru; Chiba, Kan // Pharmacogenomics Journal;2009, Vol. 9 Issue 3, p185 

    In the present study, we analyzed the function of a novel mutation (c.1628T>G, p.Leu543Trp) in the solute carrier organic anion transporter (SLCO) 1B1 gene, encoding organic anion transporting polypeptide (OATP) 1B1, which was identified in a patient with pravastatin-induced myopathy. OATP1B1...

  • Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies. Bovolenta, Matteo; Neri, Marcella; Martoni, Elena; Urciuolo, Anna; Sabatelli, Patrizia; Fabris, Marina; Grumati, Paolo; Mercuri, Eugenio; Bertini, Enrico; Merlini, Luciano; Bonaldo, Paolo; Ferlini, Alessandra; Gualandi, Francesca // BMC Medical Genetics;2010, Vol. 11, p44 

    Background: Molecular characterization of collagen-VI related myopathies currently relies on standard sequencing, which yields a detection rate approximating 75-79% in Ullrich congenital muscular dystrophy (UCMD) and 60-65% in Bethlem myopathy (BM) patients as PCR-based techniques tend to miss...

  • Multiplicity of experimental approaches to therapy for genetic muscle diseases and necessity for population screening. Nigel Laing // Journal of Muscle Research & Cell Motility;Dec2008, Vol. 29 Issue 6-8, p247 

    Abstract  Currently a multiplicity of experimental approaches to therapy for genetic muscle diseases is being investigated. These include replacement of the missing gene, manipulation of the gene message, repair of the mutation, upregulation of an alternative gene and pharmacological...

  • Truncation of Caveolin-3 causes autosomal-recessive Rippling Muscle Disease. Traverso, M.; Bruno, C.; Broccolini, A.; Sotgia, F.; Donati, M. A.; Assereto, S.; Gazzerro, E.; Lo Monaco, M.; Modoni, A.; D'Amico, A.; Gasperini, S.; Ricci, E.; Zara, F.; Lisanti, M.; Minetti, C. // Journal of Neurology, Neurosurgery & Psychiatry;Jun2008, Vol. 79 Issue 6, p735 

    The article presents a case of a truncation of Caveolin-3 (CAV3) gene which causes autosomal-recessive Rippling Muscle Disease (RMD). They have also presented the clinical, morphological and molecular analysis of a patient with autosomal-recessive RMD carrying two novel compound heterozygous...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics