Human Molecular Genetics Advance Access published online on October 3, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm269
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On noxious desmin: functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria
Human Molecular Genetics (2003) 12; 657–669; doi:10.1093/hmg/ddg060
The authors regret that the genetic analysis of the pathogenic desmin mutation was incorrect. The reported desmin mutation K239fsX242 was predicted to lead to a truncated desmin molecule with a molecular mass of 27 kDa. Since several newly generated N-terminal desmin antibodies all failed to specifically detect the truncated desmin, repeated sequencing analysis of a desmin-specific RT-PCR product from the patient's muscle RNA and subsequent direct sequencing of his genomic DNA were performed. Here, the analysis revealed a novel 3 bp-deletion (c.720_ 722delGAA) leading to the single lysine deletion mutation at position 240 (p.K240del) (Figure 1). This mutation has not been reported so far. The pathogenic potential of this mutation was addressed by transient transfection studies. In analogy to the K239fsX242 mutant the K240del mutation is incapable of forming a de novo desmin intermediate filament system in SW13 cells (data not shown) and leads to a disruption of the endogenous intermediate filament network and pathological protein aggregates in 3T3 cells (Figure 2).
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Acknowledegements
We thank Dr. Harald Bär (DKFZ, Heidelberg) for the transient transfection studies using the K240del desmin expression construct. Furthermore, we express our gratitude to Prof. Harald Herrmann (DKFZ, Heidelberg) and Prof. Roy Quinlan (University of Durham, UK) for generating antibodies specific to the N-terminus of desmin.
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