Identification of the familial cylindromatosis tumour-suppressor gene

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).     

Growth patterns in the developing brain detected by using continuum mechanical tensor maps

The dynamic nature of growth and degenerative disease processes requires the design of sensitive strategies to detect, track and quantify structural change in the brain in its full spatial and temporal complexity. Although volumes of brain substructures are known to change during development, detailed maps of these dynamic growth processes have been unavailable. Here we report the creation of spatially complex, four-dimensional quantitative maps of growth patterns in the developing human brain, detected using a tensor mapping strategy with greater spatial detail and sensitivity than previously obtainable. By repeatedly scanning children (aged 3-15 years) across time spans of up to four years, a rostro-caudal wave of growth was detected at the corpus callosum, a fibre system that relays information between brain hemispheres. Peak growth rates, in fibres innervating association and language cortices, were attenuated after puberty, and contrasted sharply with a severe, spatially localized loss of subcortical grey matter. Conversely, at ages 3-6 years, the fastest growth rates occurred in frontal networks that regulate the planning of new actions. Local rates, profiles, and principal directions of growth were visualized in each individual child.