Publication:

Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation (2005)

Author(s): Auer-Grumbach M, Schlotter-Weigel B, Lochmuller H, Strobl-Wildemann G, Auer-Grumbach P, Fischer R, Offenbacher H, Zwick EB, Robl T, Hartl G, Hartung HP, Wagner K, Windpassinger C

    Abstract: Recently, two missense mutations (N88S, S90L) in the Berardinelli-Seip congenital lipodystrophy gene have been identified in autosomal dominant distal hereditary motor neuropathy and Silver syndrome. We report the phenotypic consequences of the N88S mutation in 90 patients of 1 large Austrian family and two unrelated German families. Variation in the clinical and electrophysiological phenotype enabled us to distinguish six subtypes. In 4.4%, the disorder was not penetrant. Twenty percent of the patients were subclinically affected; some of these patients could only be detected by pathological nerve conduction studies. A distal hereditary motor neuropathy type V phenotype characterized by predominant hand muscle involvement was found in 31.1%, whereas 14.5% showed typical Silver syndrome with amyotrophy of the small hand muscles and spasticity of the lower extremities. Moreover, the phenotype present in 20% was compatible with Charcot-Marie-Tooth disease. In 10%, the clinical diagnosis of pure or complicated hereditary spastic paraparesis was made. Electrophysiological studies showed an axonal neuropathy but also chronodispersion of compound motor action potentials and conduction blocks. Sensory nerve conduction studies were rarely pathological. Our study indicates that the dominant N88S mutation in the Berardinelli-Seip congenital lipodystrophy gene 2 leads to a broad spectrum of motor neuron disorders.

    Notes: Austrian Peripheral Neuropathy Study Group

      • Date: 24-02-2005
      • Journal: Annals of Neurology
      • Volume: 57
      • Issue: 3
      • Pages: 415-424
      • Publisher: John Wiley & Sons, Inc.
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: Action Potentials/physiology/radiation effects Adolescent Adult Aged Aged, 80 and over Analysis of Variance Asparagine/genetics DNA Mutational Analysis/methods Diabetes Mellitus, Lipoatrophic/classification/ genetics/physiopathology Electric Stimulation/methods Electromyography/methods Family Health Female GTP-Binding Protein gamma Subunits/ genetics Haplotypes Humans Male Middle Aged Mutation, Missense Neural Conduction/physiology/radiation effects Pedigree Phenotype Reaction Time/physiology/radiation effects Serine/genetics Sex Factors

      Staff

      Professor Hanns Lochmuller
      Professor of Experimental Myology