We appreciate the comments by Brodehl et al1 on our recent article describing a DES mutation in a family with myofibrillar myopathy and arrhythmogenic right ventricular cardiomyopathy.2 We would like to clarify that the mutation, p.P419S in the desmin gene (DES), indeed co-segregates with the disease. When we compared the muscle biopsy findings with the presence of the p.P419S DES mutation, desmin storage was found in all investigated family members with the DES mutation but not in those without the mutation. The clinical expression of the disease was highly variable within the family. The original linkage study on this family was based on combined findings from clinical examination, electromyography and muscle biopsy.3 Three of five asymptomatic individuals were incorrectly considered affected by the myopathy based on these investigations. These three individuals showed only mild and unspecific myopathic changes and no desmin storage. Whether these individuals were affected by another mild myopathy remains to be clarified. These results demonstrate diagnostic difficulties with some forms of dominantly inherited muscle diseases, as they can display a wide clinical and morphological variability even within a given family.
In conclusion, despite the report by Brodehl et al1, we believe that the identified desmin mutation is causative for the diseases in our family, as it segregates perfectly with desmin storage in muscle. Further support for this conclusion is the finding of the same mutation segregating with desminopathy in a Spanish family.4
The authors declare no conflict of interest.
References
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