Amphiphysin 2 Gene Implicated in CNM

Mutations in a gene for the amphiphysin 2 protein may underlie at least some cases of recessively inherited centronuclear myopathy (CNM), say researchers from France, Sweden, Finland and the United Kingdom.

Anne-Sophie Nicot at the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France, and colleagues, who published their findings online Aug. 5 in Nature Genetics, studied 55 people with CNM that appeared to be inherited in a recessive pattern. In this inheritance pattern, a mutated gene from each parent is necessary to produce disease symptoms.

The researchers found three variants of the amphiphysin 2 gene that were present in four people with recessive CNM but weren’t present in 280 DNA samples from an unaffected control group. The parents of the CNM patients each had one mutated amphiphysin 2 gene, while the patients had the same mutation in both their amphiphysin 2 genes.

The researchers say the amphiphysin 2 protein normally interacts with dynamin 2, a protein known to be abnormal in another type of CNM, and that flaws in the amphiphysin 2 gene may interfere with this interaction. (Some cases of autosomal dominant CNM, in which only one mutated gene is sufficient to cause symptoms, are caused by a mutation in the dynamin 2 gene.)

The investigators say this newly identified form of CNM appears to be more severe than dominant CNM but less severe than a type of CNM known as myotubular myopathy. In that disease, the mutation is in the gene for myotubularin, which is on the X chromosome. (See “A Range of Outcomes” in Quest, September-October 2007.)

Amphiphysin-related, recessive CNM seems to begin anywhere from birth to some time in childhood, and to cause mild, slowly progressive weakness, mainly in the muscles closest to the center of the body. Cognitive impairment and respiratory impairment do not appear to be part of the disease in the patients studied.