Mizuno Toshiki, Muranishi Manabu, Torugun Torusunjian, Tango Hiromi, Nagakane Yoshinari, Kudeken Tukasa, Kawase Yuji, Kawabe Kiyokazu, Oshima Fumiko, Yaoi Takeshi, Itoh Kyoko, Fushiki Shinji, Nakagawa Masanori
Department of Molecular Neurology, Kyoto Prefectural University of Medicine, Kyoto.
Intern Med. 2008;47(23):2067-72. doi: 10.2169/internalmedicine.47.1391. Epub 2008 Dec 1.
Most previously reported mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) result in an odd number of cysteine residues within the epidermal growth factor (EGF)-like repeats in Notch3. We report here R75P mutation in two Japanese CADASIL families not directly involving cysteine residues located within the first EGF-like repeats. Probands in both families had repeated episodes of stroke, depression, dementia as well as T2 high-intensity lesions in the basal ganglia and periventricular white matter, but fewer white matter lesions in the temporal pole on MRI. These families provide new insights into the diagnosis and pathomechanisms of CADASIL.
先前报道的大多数伴有皮质下梗死和白质脑病的脑常染色体显性动脉病（CADASIL）突变会导致Notch3中表皮生长因子（EGF）样重复序列内的半胱氨酸残基数量为奇数。我们在此报告两个日本CADASIL家族中的R75P突变，该突变不直接涉及位于首个EGF样重复序列内的半胱氨酸残基。两个家族的先证者均有反复的中风、抑郁、痴呆发作，以及基底神经节和脑室周围白质的T2高信号病变，但在MRI上颞极的白质病变较少。这些家族为CADASIL的诊断和发病机制提供了新的见解。
