Novel heterozygous variants of SLC12A6 in Japanese families with Charcot-Marie-Tooth disease.
Novel heterozygous variants of SLC12A6 in Japanese families with Charcot-Marie-Tooth disease.
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DOI：
10.1002/acn3.51603
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发表时间：
2022-07
影响因子：
5.3
通讯作者：
Takashima, Hiroshi
中科院分区：
文献类型：
--
作者：
Ando, Masahiro;Higuchi, Yujiro;Yuan, Junhui;Yoshimura, Akiko;Taniguchi, Takaki;Takei, Jun;Takeuchi, Mika;Hiramatsu, Yu;Shimizu, Fumitaka;Kubota, Masaya;Takeshima, Akari;Ueda, Takehiro;Koh, Kishin;Nagaoka, Utako;Tokashiki, Takashi;Sawai, Setsu;Sakiyama, Yusuke;Hashiguchi, Akihiro;Sato, Ryota;Kanda, Takashi;Okamoto, Yuji;Takashima, Hiroshi
SLC 12 A6的隐性突变与伴有胼胝体发育不全的遗传性运动感觉神经病有关。2016年报告了与SLC 12 A6杂合变体相关的早发性周围神经病变患者。到目前为止，只有五个家族和三个变体被报道，并且谱尚不清楚。在这里，我们的目的是描述日本患者中SLC 12 A6相关Charcot-Marie-Tooth（CMT）疾病的临床和突变谱。我们从DNA微阵列中提取了SLC 12 A6变体，并对从日本各地神经科或神经儿科转诊到我们遗传实验室的2598名临床疑似CMT患者中获得的目标重测序数据进行了重新测序。并对这些患者的临床和遗传学特点进行了总结。在7个不相关的家庭，我们确定了一个以前报道的和三个新的可能致病SLC 12 A6杂合变异，以及两个变异的不确定的意义。这些患者的平均发病年龄为17.5 ± 16.1岁。关于电生理学，正中运动神经传导速度为39.6 ± 9.5 m/sec。我们第一次在三名患者中观察到智力残疾。1例患者发生癫痫，其脑部MRI显示额叶和颞叶萎缩，但白色物质和胼胝体无变化。在CMT患者中应考虑筛查SLC 12 A6基因，特别是那些患有中枢神经系统病变的患者，如认知障碍和癫痫，无论CMT亚型如何。
Recessive mutations in SLC12A6 have been linked to hereditary motor sensory neuropathy with agenesis of the corpus callosum. Patients with early‐onset peripheral neuropathy associated with SLC12A6 heterozygous variants were reported in 2016. Only five families and three variants have been reported to date, and the spectrum is unclear. Here, we aim to describe the clinical and mutation spectra of SLC12A6‐related Charcot–Marie–Tooth (CMT) disease in Japanese patients. We extracted SLC12A6 variants from our DNA microarray and targeted resequencing data obtained from 2598 patients with clinically suspected CMT who were referred to our genetic laboratory by neurological or neuropediatric departments across Japan. And we summarized the clinical and genetic features of these patients. In seven unrelated families, we identified one previously reported and three novel likely pathogenic SLC12A6 heterozygous variants, as well as two variants of uncertain significance. The mean age of onset for these patients was 17.5 ± 16.1 years. Regarding electrophysiology, the median motor nerve conduction velocity was 39.6 ± 9.5 m/sec. For the first time, we observed intellectual disability in three patients. One patient developed epilepsy, and her brain MRI revealed frontal and temporal lobe atrophy without changes in white matter and corpus callosum. Screening for the SLC12A6 gene should be considered in patients with CMT, particularly those with central nervous system lesions, such as cognitive impairment and epilepsy, regardless of the CMT subtype.
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影响因子：
7.3
作者：
Kahle KT;Flores B;Bharucha-Goebel D;Zhang J;Donkervoort S;Hegde M;Hussain G;Duran D;Liang B;Sun D;Bönnemann CG;Delpire E
通讯作者：
Delpire E
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
影响因子：
2.2
作者：
Auranen, Mari;Ylikallio, Emil;Tyynismaa, Henna
通讯作者：
Tyynismaa, Henna
影响因子：
2.8
作者：
Shi, Jiaying;Zhao, Fei;Zhang, Wei
通讯作者：
Zhang, Wei
影响因子：
3
作者：
Stojkovic, T.
通讯作者：
Stojkovic, T.