Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy

Naomi Mezaki, Takeshi Miura, Kotaro Ogaki, Makoto Eriguchi, Yuri Mizuno, Kenichi Komatsu, Hiroki Yamazaki, Natsuki Suetsugi, Sumihiro Kawajiri, Ryo Yamasaki, Takanobu Ishiguro, Takuya Konno, Hiroaki Nozaki, Kensaku Kasuga, Yasuyuki Okuma, Jun-Ichi Kira, Hideo Hara, Osamu Onodera, Takeshi Ikeuchi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere292
JournalNeurology: Genetics
Volume4
Issue number6
DOIs
Publication statusPublished - Dec 1 2018

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lamin B1
Leukoencephalopathies
Temporal Lobe
Reverse Transcription
Leukocytes
Magnetic Resonance Spectroscopy
RNA
Messenger RNA
Genes
Cognitive Dysfunction
Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant
White Matter

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Genetics(clinical)

Cite this

Mezaki, N., Miura, T., Ogaki, K., Eriguchi, M., Mizuno, Y., Komatsu, K., ... Ikeuchi, T. (2018). Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy. Neurology: Genetics, 4(6), [e292]. https://doi.org/10.1212/NXG.0000000000000292

Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy. / Mezaki, Naomi; Miura, Takeshi; Ogaki, Kotaro; Eriguchi, Makoto; Mizuno, Yuri; Komatsu, Kenichi; Yamazaki, Hiroki; Suetsugi, Natsuki; Kawajiri, Sumihiro; Yamasaki, Ryo; Ishiguro, Takanobu; Konno, Takuya; Nozaki, Hiroaki; Kasuga, Kensaku; Okuma, Yasuyuki; Kira, Jun-Ichi; Hara, Hideo; Onodera, Osamu; Ikeuchi, Takeshi.

In: Neurology: Genetics, Vol. 4, No. 6, e292, 01.12.2018.

Research output: Contribution to journalArticle

Mezaki, N, Miura, T, Ogaki, K, Eriguchi, M, Mizuno, Y, Komatsu, K, Yamazaki, H, Suetsugi, N, Kawajiri, S, Yamasaki, R, Ishiguro, T, Konno, T, Nozaki, H, Kasuga, K, Okuma, Y, Kira, J-I, Hara, H, Onodera, O & Ikeuchi, T 2018, 'Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy', Neurology: Genetics, vol. 4, no. 6, e292. https://doi.org/10.1212/NXG.0000000000000292
Mezaki, Naomi ; Miura, Takeshi ; Ogaki, Kotaro ; Eriguchi, Makoto ; Mizuno, Yuri ; Komatsu, Kenichi ; Yamazaki, Hiroki ; Suetsugi, Natsuki ; Kawajiri, Sumihiro ; Yamasaki, Ryo ; Ishiguro, Takanobu ; Konno, Takuya ; Nozaki, Hiroaki ; Kasuga, Kensaku ; Okuma, Yasuyuki ; Kira, Jun-Ichi ; Hara, Hideo ; Onodera, Osamu ; Ikeuchi, Takeshi. / Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy. In: Neurology: Genetics. 2018 ; Vol. 4, No. 6.
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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.",
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T1 - Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy

AU - Mezaki, Naomi

AU - Miura, Takeshi

AU - Ogaki, Kotaro

AU - Eriguchi, Makoto

AU - Mizuno, Yuri

AU - Komatsu, Kenichi

AU - Yamazaki, Hiroki

AU - Suetsugi, Natsuki

AU - Kawajiri, Sumihiro

AU - Yamasaki, Ryo

AU - Ishiguro, Takanobu

AU - Konno, Takuya

AU - Nozaki, Hiroaki

AU - Kasuga, Kensaku

AU - Okuma, Yasuyuki

AU - Kira, Jun-Ichi

AU - Hara, Hideo

AU - Onodera, Osamu

AU - Ikeuchi, Takeshi

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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