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GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy
Author(s) -
Okubo Masaki,
Doi Hiroshi,
Fukai Ryoko,
Fujita Atsushi,
Mitsuhashi Satomi,
Hashiguchi Shunta,
Kishida Hitaru,
Ueda Naohisa,
Morihara Keisuke,
Ogasawara Akihiro,
Kawamoto Yuko,
Takahashi Tatsuya,
Takahashi Keita,
Nakamura Haruko,
Kunii Misako,
Tada Mikiko,
Katsumoto Atsuko,
Fukuda Hiromi,
Mizuguchi Takeshi,
Miyatake Satoko,
Miyake Noriko,
Suzuki Junichiro,
Ito Yasuhiro,
Sone Jun,
Sobue Gen,
Takeuchi Hideyuki,
Matsumoto Naomichi,
Tanaka Fumiaki
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25586
Subject(s) - leukoencephalopathy , medicine , exome sequencing , pathogenesis , trinucleotide repeat expansion , exome , cadasil , pathology , disease , genetics , mutation , allele , biology , gene
Leukoencephalopathies comprise a broad spectrum of disorders, but the genetic background of adult leukoencephalopathies has rarely been assessed. In this study, we analyzed 101 Japanese patients with genetically unresolved adult leukoencephalopathy using whole‐exome sequencing and repeat‐primed polymerase chain reaction for detecting GGC expansion in NOTCH2NLC . NOTCH2NLC was recently identified as the cause of neuronal intranuclear inclusion disease. We found 12 patients with GGC expansion in NOTCH2NLC as the most frequent cause of adult leukoencephalopathy followed by NOTCH3 variants in our cohort. Furthermore, we found 1 case with de novo GGC expansion, which might explain the underlying pathogenesis of sporadic cases. ANN NEUROL 2019;86:962–968