Two Japanese CADASIL Families Exhibiting Notch3 Mutation R75P Not Involving Cysteine Residue

Toshiki Mizuno; Manabu Muranishi; Torusunjian Torugun; Hiromi Tango; Yoshinari Nagakane; Tukasa Kudeken; Yuji Kawase; Kiyokazu Kawabe; Fumiko Oshima; Takeshi Yaoi; Kyoko Itoh; Shinji Fushiki; Masanori Nakagawa

doi:10.2169/internalmedicine.47.1391

CASE REPORTS

Two Japanese CADASIL Families Exhibiting Notch3 Mutation R75P Not Involving Cysteine Residue

Toshiki Mizuno, Manabu Muranishi, Torusunjian Torugun, Hiromi Tango, Yoshinari Nagakane, Tukasa Kudeken, Yuji Kawase, Kiyokazu Kawabe, Fumiko Oshima, Takeshi Yaoi, Kyoko Itoh, Shinji Fushiki, Masanori Nakagawa

Author information

Toshiki Mizuno
Department of Molecular Neurology, Kyoto Prefectural University of Medicine
Manabu Muranishi
Department of Molecular Neurology, Kyoto Prefectural University of Medicine
Torusunjian Torugun
Department of Molecular Neurology, Kyoto Prefectural University of Medicine
Hiromi Tango
Department of Molecular Neurology, Kyoto Prefectural University of Medicine
Yoshinari Nagakane
Department of Molecular Neurology, Kyoto Prefectural University of Medicine
Tukasa Kudeken
Department of Neurology, Oomori Hospital, Toho University
Yuji Kawase
Department of Neurology, Oomori Hospital, Toho University
Kiyokazu Kawabe
Department of Neurology, Oomori Hospital, Toho University
Fumiko Oshima
Department of Neurology, Kyoto First Red Cross Hospital
Takeshi Yaoi
Department of Pathology & Applied Neurobiology, Kyoto Prefectural University of Medicine
Kyoko Itoh
Department of Pathology & Applied Neurobiology, Kyoto Prefectural University of Medicine
Shinji Fushiki
Department of Pathology & Applied Neurobiology, Kyoto Prefectural University of Medicine
Masanori Nakagawa
Department of Molecular Neurology, Kyoto Prefectural University of Medicine

Keywords: CADASIL, Notch3, EGF-like repeat, cysteine, white matter lesion, GOM

JOURNAL OPEN ACCESS

2008 Volume 47 Issue 23 Pages 2067-2072

DOI https://doi.org/10.2169/internalmedicine.47.1391

Details

Abstract

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.

Corresponding author

Register with J-STAGE for free!