Editorial

The cover of this issue relates to a review by Christian Hübner and Ingo Kurth of a class of proteins that confer curvature to intracellular membranes, and their involvement in neurological disease. Endoplasmic reticulum, the Golgi apparatus, mitochondria and other subcellular organelles all have characteristic shapes, which arise in large part from insertion of wedge-shaped proteins into lipid bilayers. Hübner and Kurth explore the emerging theme that mutations of such proteins cause degeneration of central or peripheral axons. Why long axons are particularly vulnerable is incompletely understood. Strikingly, distinct mutations of some of the genes involved can lead either to hereditary spastic paraplegia or to sensory neuropathy. Clearly, much work remains to be done to resolve the cellular mechanisms of these diseases and identify therapeutic targets. I shall take this opportunity to propose the term camptolemmopathies, from the Greek for bent (kamptos) and husk (lemma), as a collective noun to describe them.

Mouse knock-in mutants provide a potentially powerful insight into mechanisms of genetic diseases due to missense mutations, although phenotypes do not always recapitulate the human disorders. An alternative application of mouse genetics is to screen randomly mutagenized mice for phenotypes that resemble human diseases. In this issue Corrochano Sanchez and co-workers describe a remarkable convergence between such a forward genetic screen and clinical neurogenetics. They report a missense mutation in the muscle sodium channel gene SCN4A in a family affected by myotonia and periodic paralysis. The identical amino acid change was identified in the mouse orthologue, in a strain that exhibits spontaneous episodes of hind limb paralysis, yielding a powerful model to study the pathophysiology of the disease.

Also in this issue, Johann Böhm and colleagues identify BIN1 as a gene for dominant centronuclear myopathy. Ianai Fishbein, Yien-Ming Kuo and co-workers show that heterozygosity for a glucocerebrosidase mutation associated with Gaucher’s disease interferes with α-synuclein degradation and exacerbates a mouse model of Parkinson’s disease, providing mechanistic support for the genetic association between these diseases. Mario Dorostkar, Steffen Burgold and co-workers report promising preclinical results of immunotherapy targeted to oligomeric amyloid-β.

Elsewhere in this issue, Kristi Clark and colleagues use serial MRI scans in a cohort of Norwegian children to argue that the earliest neuroanatomical differences in dyslexia are in primary sensory cortex (see also the Scientific Commentary by Usha Goswami). Dyslexia is also the subject of a Book Review by Franck Ramus of The Dyslexia Debate by Elliott and Grigorenko, a book that is making waves by questioning the usefulness of dyslexia as a diagnostic label. Ramus provides a robust defence of the concept of dyslexia as distinct from general reading disability.