Multi-type RFC1 repeat expansions as the most common cause of hereditary sensory and autonomic neuropathy.
Multi-type RFC1 repeat expansions as the most common cause of hereditary sensory and autonomic neuropathy.
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DOI：
10.3389/fneur.2022.986504
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发表时间：
2022
影响因子：
3.4
通讯作者：
Takashima, Hiroshi
中科院分区：
文献类型：
--
作者：
Yuan, Jun-Hui;Higuchi, Yujiro;Ando, Masahiro;Matsuura, Eiji;Hashiguchi, Akihiro;Yoshimura, Akiko;Nakamura, Tomonori;Sakiyama, Yusuke;Mitsui, Jun;Ishiura, Hiroyuki;Tsuji, Shoji;Takashima, Hiroshi
RFC 1和NOTCH 2NLC基因内的非编码重复序列扩增最近被认为与多系统神经退行性疾病有关，这也为尚未确诊的遗传性周围神经病患者提供了线索。本研究的目的是确定遗传性感觉和自主神经病变（HSAN）患者的遗传基础。我们从日本多个地区收集了79份临床疑似HSAN的无关DNA样本。首先使用基因组测序和全外显子组测序进行突变筛选。从WNK 1/HSN 2（6例）、SCN 9A（3例）、NTRK 1（3例）和DNMT 1（2例）的基因中鉴定出致病性/可能致病性变体。随后，应用长距离侧翼PCR和重复引物PCR分析RFC 1和NOTCH 2NLC中的重复扩增。在20例成人HSAN患者中检测到双等位基因RFC 1重复扩增，包括[（AAGGG）exp/（AAGGG）exp]（8例）、[（ACAGG）exp/（ACAGG）exp]（8例）和[（AAGGG）exp/（ACAGG）exp]（4例）。1例NOTCH 2NLC中发现GGC重复扩增。基于单核苷酸变异的单倍型分析的患者窝藏疾病相关的重复扩增RFC 1显示不同的重复基因型的亚组之间的可区分的单倍型。这些发现基本上重新定义了HSAN的遗传谱，其中多种类型的RFC 1重复扩增占所有患者的25.3%，突出了遗传筛查的必要性，特别是对于成人发病的患者。
Non-coding repeat expansions within RFC1 and NOTCH2NLC genes have lately been linked to multisystem neurodegenerative diseases, which also shed light on yet undiagnosed patients with inherited peripheral neuropathies. The aim of this study was to identify the genetic basis of patients with hereditary sensory and autonomic neuropathy (HSAN). We collected 79 unrelated DNA samples clinically suspected with HSAN from multiple regions of Japan. Mutation screening was first performed using gene panel sequencing and whole-exome sequencing. Pathogenic/likely pathogenic variants were identified from genes of WNK1/HSN2 (6 cases), SCN9A (3 cases), NTRK1 (3 cases), and DNMT1 (2 cases). Subsequently, long-range flanking PCR and repeat-primed PCR were applied to analyze repeat expansions in RFC1 and NOTCH2NLC. Bi-allelic RFC1 repeat expansions were detected from 20 adult-onset HSAN patients, consisting of [(AAGGG)exp/(AAGGG)exp] (8 cases), [(ACAGG)exp/(ACAGG)exp] (8 cases), and [(AAGGG)exp/(ACAGG)exp] (4 cases). GGC repeat expansion in NOTCH2NLC was found in 1 case. Single-nucleotide variant-based haplotype analysis of patients harboring disease-associated repeat expansions in RFC1 revealed distinguishable haplotypes among subgroups with different repeat genotypes. These findings substantially redefine the genetic spectrum of HSAN, where multi-type RFC1 repeat expansions account for 25.3% of all patients, highlighting the necessity of genetic screening, particularly for adult-onset patients.
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影响因子：
11.2
作者：
Higuchi, Yujiro;Hashiguchi, Akihiro;Yuan, Junhui;Yoshimura, Akiko;Mitsui, Jun;Ishiura, Hiroyuki;Tanaka, Masaki;Ishihara, Satoshi;Tanabe, Hajime;Nozuma, Satoshi;Okamoto, Yuji;Matsuura, Eiji;Ohkubo, Ryuichi;Inamizu, Saeko;Shiraishi, Wataru;Yamasaki, Ryo;Ohyagi, Yasumasa;Kira, Jun-ichi;Oya, Yasushi;Yabe, Hayato;Nishikawa, Noriko;Tobisawa, Shinsuke;Matsuda, Nozomu;Masuda, Masayuki;Kugimoto, Chiharu;Fukushima, Kazuhiro;Yano, Satoshi;Yoshimura, Jun;Doi, Koichiro;Nakagawa, Masanori;Morishita, Shinichi;Tsuji, Shoji;Takashima, Hiroshi
通讯作者：
Takashima, Hiroshi
DOI：
10.1093/brain/awp198
发表时间：
2009-10
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Rotthier A;Baets J;De Vriendt E;Jacobs A;Auer-Grumbach M;Lévy N;Bonello-Palot N;Kilic SS;Weis J;Nascimento A;Swinkels M;Kruyt MC;Jordanova A;De Jonghe P;Timmerman V
通讯作者：
Timmerman V
影响因子：
3.5
作者：
Tsuji, Shoji;Onodera, Osamu;Nishizawa, Masatoyo
通讯作者：
Nishizawa, Masatoyo
影响因子：
5.3
作者：
Miura, Y;Mardy, S;Indo, Y
通讯作者：
Indo, Y
影响因子：
14.9
作者：
Tadaka S;Hishinuma E;Komaki S;Motoike IN;Kawashima J;Saigusa D;Inoue J;Takayama J;Okamura Y;Aoki Y;Shirota M;Otsuki A;Katsuoka F;Shimizu A;Tamiya G;Koshiba S;Sasaki M;Yamamoto M;Kinoshita K
通讯作者：
Kinoshita K