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
Department of Molecular Genetics (N.M., T.M., T. Ishiguro, K. Kasuga, T. Ikeuchi) and Department of Neurology (N.M., T.M., T. Ishiguro, T.K., O.O.), Brain Research Institute, Niigata University; Department of Neurology (K.O., S.K., Y.O.), Juntendo University Shizuoka Hospital; Division of Neurology, Department of Internal Medicine (M.E., N.S., H.H.), Faculty of Medicine, Saga University; Department of Neurology (Y.M., R.Y., J.-I.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University; Department of Neurology (K. Komatsu, H.Y.), Kitano Hospital, The Tazuke Kofukai Medical Research Institute; and Medical Technology (H.N.), Graduate School of Health Sciences, Niigata University.
Neurol Genet. 2018 Dec 7;4(6):e292. doi: 10.1212/NXG.0000000000000292. eCollection 2018 Dec.
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 ().
Ninety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of and its upstream genes. We examined expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed.
We identified 4 patients from 3 families with duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of in patients with duplication was significantly increased. The clinical features of our patients with 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 . 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.
We identified 4 Japanese families with ADLD carrying duplication or deletion upstream of . There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of .
对携带核纤层蛋白B1（）上游重复和缺失的常染色体显性成人起病型脱髓鞘性脑白质营养不良（ADLD）患者的遗传和临床特征进行描述。
对93例病因不明的成人起病型白质脑病患者进行基因分析，检测其和上游基因的拷贝数。使用从外周血白细胞中提取的总RNA，通过逆转录定量聚合酶链反应检测的表达。对ADLD患者的临床和磁共振成像（MRI）特征进行回顾性分析。
我们从3个家族中鉴定出4例携带重复的患者。重复的基因组区域与先前报道的不同。携带重复的患者中的mRNA表达水平显著升高。我们携带重复的患者的临床特征与先前报道的相似，但认知障碍的发生率较高。我们从1个家族中发现2例携带上游249 kb基因组缺失的患者。与携带重复的患者相比，携带缺失的患者发病相对较早，认知障碍更突出，自主神经症状较少。与先前报道的携带缺失的家族相比，我们携带缺失的患者可能具有小脑症状和病变的特征。携带缺失的患者的MRI显示白质病变广泛分布，包括颞前区。
我们鉴定出4个日本ADLD家族，其携带上游重复或缺失。携带重复的患者与携带上游缺失的患者在临床和MRI特征上存在差异。
