Mutations, but not germline. Many of the genetic alterations that we aim to investigate within the EuroEPINOMICS projects are so-called germline mutations. In the case of de novo events, these mutations have occurred in the germ cells themselves or in very early development. In the case of autosomal dominant or recessive inheritance, the mutations have been transmitted from parents. In either case, the mutation can be found in every cell of the body. Cancer research is mainly focussed on somatic mutations, which give rise to malignant transformation in already differentiated tissues. In fact, many of the techniques that we currently use in neurogenetics were developed to study somatic genetic aberrations. Array comparative genomic hybridization for example, had initially been established for these purposes before expanding the focus to germline microdeletions and microduplications. While the role of somatic mutations in cancer research is well established, the role somatic rather than germline genetic alterations play in other disorders is mainly speculative. Some initial evidence for somatic point mutations has recently been found in Proteus syndrome, a rare overgrowth syndrome. Activating somatic mutations in AKT1 have recently been identified in this disorder. A recent paper by Lee and colleagues now identifies mutations in several genes in the mTOR pathway in patients with hemimegalencephaly, a severe form of brain malformation. Continue reading →