Clinical and genetic heterogeneity in autosomal recessive nemaline myopathy

Carina Wallgren-Pettersson, Katarina Pelin, Pirta Hilpelä, Kati Donner, Berardino Porfirio, Claudio Graziano, Kathryn J. Swoboda, Michel Fardeau, J. Andoni Urtizberea, Francesco Muntoni, Caroline Sewry, Victor Dubowitz, Susan Iannaccone, Carlo Minetti, Marina Pedemonte, Marco Seri, Roberto Cusano, Martin Lammens, Avril Castagna-Sloane, Alan H. BeggsNigel G. Laing, Albert De La Chapelle

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Autosomal recessive nemaline (rod) myopathy is clinically and genetically heterogeneous. A clinically distinct, typical form, with onset in infancy and a non-progressive or slowly progressive course, has been assigned to a region on chromosome 2q22 harbouring the nebulin gene. Mutations have now been found in this gene, confirming its causative role. The gene for slow tropomyosin TPM3 on chromosome 1q21, previously found to cause a dominantly inherited form, has recently been found to be homozygously mutated in one severe consanguineous case. Here we wished to determine the degree of genetic homogeneity or heterogeneity of autosomal recessive nemaline myopathy by linkage analysis of 45 families from 10 countries. Forty-one of the families showed linkage results compatible with linkage to markers in the nebulin region, the highest combined lod scores at zero recombination being 14.13 for the marker D2S2236. We found no indication of genetic heterogeneity for the typical form of nemaline myopathy. In four families with more severe forms of nemaline myopathy, however, linkage to both the nebulin and the TPM3 locus was excluded. Our results indicate that at least three genetic loci exist for autosomal recessive nemaline myopathy. Studies of additional families are needed to localise the as yet unknown causative genes, and to fully elucidate genotype-phenotype correlations. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)564-572
Number of pages9
JournalNeuromuscular Disorders
Issue number8
StatePublished - Dec 1 1999


  • Autosomal recessive
  • Clinical forms
  • Congenital myopathy
  • Genetic heterogeneity
  • Genetic loci
  • Locus heterogeneity
  • Nemaline (rod) myopathy
  • Nemaline myopathy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)


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