The age of single-gene neurological disorders is not dead.

term follow up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis. et al. Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation. microarrays identify key mediators of autoimmune brain inflammation. The natural history of multiple sclerosis: a geographically based study. 9: Observations on the progressive phase of the disease. Evidence for a two-stage disability progression in multiple sclerosis.cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. et al. The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability. of multiple sclerosis relapses on progression diminishes with time. The natural history of multiple sclerosis: a geographically based study. 1. Clinical course and disability. The age of single-gene neurological disorders is not dead This edition of Brain sees the first of a series of articles describing new genes responsible for inherited neurological disease, thus expanding the clinical neurogenetics portfolio. Sebahattin Cirak from the Institute of Child Health in London led a transcontinental consortium of clinical and basic science researchers who map the locus for a gene responsible for an autosomal dominant distal myopathy (Cirak et al., 2010). Their work casts new light on the disease mechanisms of these poorly understood disorders; but at the same time, they broaden concepts on the potential mechanisms involved. Distal myopathies provide a classical example of the way that molecular genetics has revolutionized classifications in clinical neurology (Table 1). First described in the early part of the last century (Gowers, 1902), they were the focus of that old neuro-logical chestnut 'is the distal weakness due to muscle or nerve dysfunction?' and were latterly subdivided into discrete entities based on astute clinical examination (reviewed in Barohn et al., 1998). Early gene mapping studies identified several loci, highlighted the likely aetiological heterogeneity and led to the further delineation of different clinical groups (Udd, 2009). A major subgroup was associated with pathological myofibrils (myfibrillar myopathies) (Udd, 2009), overlapping with inherited limb girdle syndromes. Positional cloning and candidate gene analysis led to the rounding-up of some obvious culprits [MYO7, the myosin heavy chain 7 gene (Meredith et al., 2004) and fast IIa myosin as recently published in Brain (Tajsharghi et al., 2010)] and provided a satisfying explanation for the muscle …