A novel mutation and large size polymorphism affecting the V2 domain of keratin 1 in an African-American family with severe, diffuse palmoplantar keratoderma of the ichthyosis hystrix Curth-Macklin type.

Keratin gene mutations affecting nonhelical head and tail domains are not usually associated with prominent skin blistering and keratin filament clumping. Instead, they have been associated with several distinct clinical phenotypes, such as epidermolysis bullosa simplex with mottled pigmentation (mutation P25L in the V1 domain of keratin 5), epidermolysis bullosa simplex with migratory circinate erythema (frameshift mutation c1649delG in the V2 domain of keratin 5), striate palmoplantar keratoderma (PPK), and ichthyosis hystrix Curth-Macklin (different frameshift mutations in the V2 domain of keratin 1 (K1)). We have studied a family with severe, diffuse, nonepidermolytic PPK and verrucous hyperkeratotic plaques over the joints and in flexures and identified a new KRT1 gene mutation that is predicted to completely alter the K1 tail domain. In addition, a new K1 size polymorphism has been detected, which is especially prevalent among the African-American population. These results further emphasize the functional importance of the nonhelical tail domain in keratin molecules despite the obvious variability in the number of glycine loop motifs and underscore the broad phenotypic spectrum of disorders due to dominant keratin tail mutations.

Brush allodynia in hospitalized headache patients.

OBJECTIVE: To describe the incidence and time course of dynamic mechanical allodynia (brush allodynia, BA) in an inpatient headache population. BACKGROUND: Four types of cutaneous allodynia (heat, cold, static mechanical [pressure], and dynamic mechanical [brush] allodynia) can be studied in headache patients. In episodic migraineurs, the development of cutaneous allodynia heralds a change in treatment response. However, little is known about the functional significance of BA, and little is known about the frequency of any type of cutaneous allodynia among patients with chronic or more severe headache disorders. Methods.-The protocol was approved by the institutional review board of our university hospital. A total of 78 subjects were tested for allodynia on days 1, 3, and 5 of an inpatient hospital stay using a 4 x 4 folded gauze pad stroked 10 times at three bilateral sites (forehead, jaw, and forearm). Subjects were queried about the signs and symptoms of their headaches. Headache intensity was graded with a verbal 11-point scale and the intensity of allodynia was graded using a 10 cm visual analog scale. RESULTS: A total of 61 patients had transformed migraine (TM). BA was present at some point during the hospitalization in 32 subjects (41%). Neither age nor duration of daily headache correlated with headache severity. Headache intensity, a history of sensory symptoms or weakness, and subjective blurred vision accompanying the headache correlated with the presence of BA (P< or = .05). Unilateral headaches were more likely to be associated with BA (P = .01), independent of headache severity. When headache was unilateral, BA was greatest ipsilateral to the headache. BA did not influence outcome as measured by length of stay or the likelihood of being discharged headache-free. The rate of decline of headache intensity and allodynia score were similar. CONCLUSION: BA is common in hospitalized headache patients. Subjects with more severe unilateral headaches were more likely to have BA. The presence of BA did not predict treatment failure in an inpatient setting.