Neurogenetics

, Volume 8, Issue 2, pp 137–142

Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy

  • Sabine Rudnik-Schöneborn
  • Elke Botzenhart
  • Thomas Eggermann
  • Jan Senderek
  • Benedikt G. H. Schoser
  • Rolf Schröder
  • Manfred Wehnert
  • Brunhilde Wirth
  • Klaus Zerres
Original Article

DOI: 10.1007/s10048-006-0070-0

Cite this article as:
Rudnik-Schöneborn, S., Botzenhart, E., Eggermann, T. et al. Neurogenetics (2007) 8: 137. doi:10.1007/s10048-006-0070-0

Abstract

The molecular basis of autosomal dominant spinal muscular atrophy (AD-SMA) is largely unknown. Because the phenotypic spectrum of diseases caused by LMNA mutations is extremely broad and includes myopathies, neuropathies, and cardiomyopathies designated as class 1 laminopathies, we sequenced the LMNA gene in index patients with the clinical picture of proximal SMA, who had a family history suggestive of autosomal dominant inheritance. Among the 19 families investigated, two showed pathogenic mutations of the LMNA gene, resulting in the diagnosis of a class 1 laminopathy in about 10% of our series. We found one novel truncating mutation (c.1477C > T, Q493X) and one previously described missense mutation (c.1130G > T, R377H) in the LMNA gene of two unrelated patients with adult-onset proximal SMA followed by cardiac involvement 14 and 22 years after the onset of weakness. The pedigrees of both families revealed a high frequency of cardiac abnormalities or sudden deaths. Our findings extend the spectrum of laminopathies and are of relevance for genetic counseling and clinical care of families presenting with adult-onset proximal SMA. Particularly, if neurogenic atrophy is combined with a cardiac disease in a family, this should prompt LMNA mutation analysis.

Keywords

Autosomal dominant spinal muscular atrophyEmery–Dreifuss muscular dystrophyLMNA mutationCardiac complications

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Sabine Rudnik-Schöneborn
    • 1
  • Elke Botzenhart
    • 1
  • Thomas Eggermann
    • 1
  • Jan Senderek
    • 1
  • Benedikt G. H. Schoser
    • 2
  • Rolf Schröder
    • 3
  • Manfred Wehnert
    • 4
  • Brunhilde Wirth
    • 5
  • Klaus Zerres
    • 1
  1. 1.Institute for Human GeneticsRWTH Aachen UniversityAachenGermany
  2. 2.Friedrich-Baur-InstituteUniversity of MunichMunichGermany
  3. 3.Clinic of NeurologyUniversity of BonnBonnGermany
  4. 4.Institute for Human GeneticsUniversity of GreifswaldGreifswaldGermany
  5. 5.Institute for Human Genetics, Institute of Genetics and Center for Molecular Medicine CologneUniversity of CologneCologneGermany