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. 2019 Dec;86(6):962-968.
doi: 10.1002/ana.25586. Epub 2019 Oct 22.

GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy

Masaki Okubo  1 , Hiroshi Doi  1 , Ryoko Fukai  1 , Atsushi Fujita  2 , Satomi Mitsuhashi  2 , Shunta Hashiguchi  1 , Hitaru Kishida  3 , Naohisa Ueda  3 , Keisuke Morihara  1 , Akihiro Ogasawara  1 , Yuko Kawamoto  1 , Tatsuya Takahashi  4 , Keita Takahashi  1 , Haruko Nakamura  1 , Misako Kunii  1 , Mikiko Tada  1 , Atsuko Katsumoto  1 , Hiromi Fukuda  1   2 , Takeshi Mizuguchi  2 , Satoko Miyatake  2 , Noriko Miyake  2 , Junichiro Suzuki  5 , Yasuhiro Ito  5 , Jun Sone  6   7 , Gen Sobue  7   8   9 , Hideyuki Takeuchi  1 , Naomichi Matsumoto  2 , Fumiaki Tanaka  1
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GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy

Masaki Okubo et al. Ann Neurol. 2019 Dec.

Abstract

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.

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References

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    1. Vanderver A, Simons C, Helman G, et al. Whole exome sequencing in patients with white matter abnormalities. Ann Neurol 2016;79:1031-1037.
    1. Sone J, Mitsuhashi S, Fujita A, et al. Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nat Genet 2019;51:1215-1221.
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