AChR deficiency due to ε-subunit mutations: Two common mutations in the Netherlands

textabstractCongenital myasthenic syndromes are a clinically and genetically heterogeneous group of hereditary disorders affecting neuromuscular transmission. We have identified mutations within the acetylcholine receptor (AChR) ε-subunit gene underlying congenital myasthenic syndromes in nine patients (seven kinships) of Dutch origin. Previously reported mutations ε1369delG and εR311Q were found to be common; ε1369delG was present on at least one allele in seven of the nine patients, and εR311Q in six. Phenotypes ranged from relatively mild ptosis and external ophthalmoplegia to generalized myasthenia. The common occurrence of εR311Q and ε1369delG suggests a possible founder for each of these mutations originating in North Western Europe, possibly in Holland. Knowledge of the ethnic or geographic origin within Europe of AChR deficiency patients can help in targeting genetic screening and it may be possible to provide a rapid genetic diagnosis for patients of Dutch origin by screening first for εR311Q and ε1369delG