-
Kazuki Kijima,
Chikahiko Numakura,
Hiroko Izumino,
Kazuo Umetsu,
Atsuo Nezu,
Toshihide Shiiki,
Masafumi Ogawa,
Yoshito Ishizaki, Takeshi Kitamura,
Yasunobu Shozawa,
Kiyoshi Hayasaka
[show abstract]
[hide abstract]
ABSTRACT: Charcot-Marie-Tooth disease (CMT) has been classified into two types, CMT1 and CMT2, demyelinating and axonal forms, respectively. CMT2 has been further subdivided into eight groups by linkage studies. CMT2A is linked to chromosome 1p35-p36 and mutation in the kinesin family member 1B-beta (KIF1B) gene had been reported in one pedigree. However, no mutation in KIF1B was detected in other pedigrees with CMT2A and the mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) gene were recently detected in those pedigrees. MFN2, a mitochondrial transmembrane GTPase, regulates the mitochondrial network architecture by fusion of mitochondria. We studied MFN2 in 81 Japanese patients with axonal or unclassified CMT and detected seven mutations in seven unrelated patients. Six of them were novel and one of them was a de novo mutation. Most mutations locate within or immediately upstream of the GTPase domain or within two coiled-coil domains, which are critical for the functioning or mitochondrial targeting of MFN2. Formation of a mitochondrial network would be required to maintain the functional peripheral nerve axon.
Human Genetics 02/2005; 116(1-2):23-7. · 5.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine whether magnetization transfer imaging (MTI) demonstrates abnormalities in the brain structures of patients with multiple system atrophy (MSA), we examined 12 patients with clinically probable MSA and 11 control subjects. We calculated magnetization transfer ratios (MTRs) using region of interest analysis from MTI and assessed abnormal signal changes on T2-weighted images. MTRs of the base of the pons, middle cerebellar peduncle, putamen, and white matter of the precentral gyrus were significantly lower in the MSA patients than in the controls. Abnormal signal changes on T2-weighted images were observed in the base of the pons (n = 6), middle cerebellar peduncle (n = 7), and putamen (n = 7). MTRs of regions with abnormal signals were significantly lower than those of regions without abnormal signals and those in the controls. Even the MTRs of the regions without abnormal signals were lower than those in the controls. MTRs of the pyramidal tract, including white matter of the precentral gyrus, posterior limb of the internal capsule, cerebral peduncle, and base of the pons, were significantly lower in patients with pyramidal tract sign (n = 7) than in the controls. Patients with asymmetrical parkinsonism (n = 5) showed significantly lower MTRs in the putamen contralateral to the predominant side of parkinsonian symptoms than the ipsilateral side, although asymmetry of abnormal signal changes on T2-weighted images was not evident in more than half of those patients. This study showed that MTI demonstrates abnormalities in the brains of patients with MSA that seem to reflect underlying pathological changes and that the pathological changes detected by MTI seem to give rise to clinical symptoms. This study also showed that the abnormalities are detected more sensitively and over a larger area by MTI than by conventional magnetic resonance imaging.
NeuroImage 12/2002; 17(3):1572-8. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine whether patients with myotonic dystrophy (MyD) have structural changes in the cerebral white matter, we performed magnetization transfer (MT) imaging of the cerebral white matter in 14 MyD patients and 11 age-matched normal controls. We calculated MT ratios in both the white matter lesions (WMLs) and the normal-appearing white matter (NAWM) of MyD patients using region of interest (ROI) analysis. MT ratios in WMLs were markedly decreased, and all ROIs in NAWM also showed significantly lower MT ratios in MyD patients than in normal controls. The average MT ratio of all ROIs in WMLs and NAWM in each patient showed a significant negative correlation with duration of illness, but not with the patient's age or age at onset. The results of the present study indicate not only the presence of pathological changes in WMLs but also the widespread involvement of NAWM in MyD patients. The results also suggest that structural changes in the white matter may be progressive during the clinical course of MyD.
Journal of the Neurological Sciences 02/2002; 193(2):111-6. · 2.35 Impact Factor
