@article{be332afcd28c48918110a81eccba5616,
title = "Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy",
abstract = "Objective To characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 (LMNB1). Methods Ninety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of LMNB1 and its upstream genes. We examined LMNB1 expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed. Results We identified 4 patients from 3 families with LMNB1 duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of LMNB1 in patients with duplication was significantly increased. The clinical features of our patients with LMNB1 duplication were similar to those reported previously, except for the high frequency of cognitive impairment in our patients. We found 2 patients from 1 family carrying a 249-kb genomic deletion upstream of LMNB1. Patients with the deletion exhibited relatively earlier onset, more prominent cognitive impairment, and fewer autonomic symptoms than patients with duplication. The presence of cerebellar symptoms and lesions may be characteristic in our patients with the deletion compared with the previously reported family with the deletion. Magnetic resonance images of patients with the deletion exhibited a widespread distribution of white matter lesions including the anterior temporal region. Conclusions We identified 4 Japanese families with ADLD carrying duplication or deletion upstream of LMNB1. There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of LMNB1.",
author = "Naomi Mezaki and Takeshi Miura and Kotaro Ogaki and Makoto Eriguchi and Yuri Mizuno and Kenichi Komatsu and Hiroki Yamazaki and Natsuki Suetsugi and Sumihiro Kawajiri and Ryo Yamasaki and Takanobu Ishiguro and Takuya Konno and Hiroaki Nozaki and Kensaku Kasuga and Yasuyuki Okuma and Kira, {Jun Ichi} and Hideo Hara and Osamu Onodera and Takeshi Ikeuchi",
note = "Funding Information: N. Mezaki has received foundation and society research support from the Tsubaki Memorial Foundation and JA Niigata Kouseiren grant. T. Miura, K. Ogaki, M. Eriguchi, Y. Mizuno, K. Komatsu, H. Yamazaki, N. Suetsugi, and S. Kawajiri report no disclosure. R. Yamasaki serves on the editorial board of Clinical and Experimental Neuroimmunology. T. Ishiguro, T. Konno, and H. Nozaki report no disclosure. K. Kasuga has received research support from the Japan Society for the Promotion of Science. Y. Okuma reports no disclosures. J.-I. Kira has served on the editorial boards of Multiple Sclerosis, BMC Medicine, Journal of the Neurological Sciences, Multiple Sclerosis and Related Disorders, PLoS One, Acta Neuropathologica Communications, and Clinical and Experimental Neuroimmunology; has provided consultancy for Biogen Idec Japan; and has received research support from governmental entities the Ministry of Health, Labour and Welfare, Japan Agency for Medical Research and Development, and the MEXT KAKENHI program. H. Hara has received funding for travel from Novartis and for speaker honoraria from Eisai and has received Grant-in-Aid for Scientific Research. O. Onodera has received funding for speaker honoraria from Kyowa Hakko Kirin Co., Ltd., Bristol-Myers Squibb, Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma, Takeda, Daiichi-Sankyo, Fujifilm, Sanofi, and FP-Pharma and has received governmental entity research support for Scientific Research from a Grant-in-Aid from the Research Committee for Hereditary Cerebral Small Vessel Diseases, and from the Ministry of Health, Labour and Welfare of Japan. T. Ikeuchi has served on the editorial board of Parkinsonism and Related Disorders; has acted as a consultant for Janssen Pharmaceuticals Inc. and Chugai Pharmaceutical Co. Ltd.; serves on the speakers{\textquoteright} bureaus of Daiichi Sankyo, Eisai, Ono Pharmaceutical Co. Ltd., Novartis, and Takeda; and has received governmental entity research support from KAKENHI and the Ministry of Health. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG. Funding Information: Supported in part by grant-in-aid (JP16H01331 and 26117506 to T.Ikeuchi) from the Japan Society for the Promotion of Science, a grant-in-aid for Research on Intractable Disease from the Japanese Ministry of Health, Labour and Welfare, Japan (12103055 to T.Ikeuchi and O.O.), a grant-in-aid (18kk0205009 to T.Ikeuchi) from Japan Agency for Medical Research and Development, and a grant from the Tsubaki Memorial Foundation (to N.M.). Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1212/NXG.0000000000000292",
language = "English",
volume = "4",
journal = "Neurology: Genetics",
issn = "2376-7839",
publisher = "Lippincott Williams and Wilkins",
number = "6",
}