Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
A reduced habituation of
averaged laser–evoked potential
(LEP) amplitudes was previously
found in migraine patients. The aim
of the present study was to assess
the habituation of single LEP
responses and pain sensation during
the interictal phase in migraine
patients. Fourteen migraine patients
were compared with ten control
subjects. The pain stimulus was
laser pulses, generated by CO
2
laser, delivered to right supraorbital
zone. Patients were evaluated during
attack–free conditions. The LEP
habituation was studied by measuring
the changes of LEP amplitudes
across and within three consecutive
repetitions of 21 non–averaged trials.
In migraine patients the N2–P2
wave amplitudes did not show a
tendency toward habituation across
and, above all, within the three repetitions.
Anomalous behaviour of
nociceptive cortex during the interictal
phase of migraine may predispose
patients to headache occurrence
and persistence.
CM seems to be characterized by a distinctive pattern of cortical elaboration of pain, with a prevalent activation of the rostral portion of the ACC: our results suggest that this may be a predisposing factor to migraine chronicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.