ATP1A3 mosaicism in families with alternating hemiplegia of childhood
ATP1A3 mosaicism in families with alternating hemiplegia of childhood
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儿童交替性偏瘫家族中的 ATP1A3 嵌合现象
DOI：
10.1111/cge.13539
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发表时间：
2019-04
影响因子：
3.5
通讯作者：
Zhang Yuehua
中科院分区：
文献类型：
--
作者：
Yang Xiaoling;Yang Xiaoxu;Chen Jiaoyang;Li Shupin;Zeng Qi;Huang August Y.;Ye Adam Y.;Yu Zhe;Wang Sheng;Jiang Yuwu;Wu Xiru;Wu Qixi;Wei Liping;Zhang Yuehua
儿童交替性偏瘫（AHC）是一种罕见且严重的神经发育障碍，其特征是反复发作的偏瘫。大多数 AHC 病例是散发性的，由 ATP1A3 新致病变异引起。本研究的目的是确定中国人群中 ATP1A3 致病性变异的起源。在105名先证者中，包括101名散发病例和4名家族性病例，共鉴定出98名携带ATP1A3致病变异的患者，其中96.8%被确诊为新发病例。应用微滴数字聚合酶链式反应检测 80 个可用家族中的 ATP1A3 嵌合体。在血液样本中，四名无症状父母（包括两名父亲和两名母亲）以及一名表型较轻的先证者被鉴定为嵌合体。在多个组织中发现了六种（7.5％）亲本嵌合体，其中包括先前在血液中发现的四种以及从父亲精子中发现的另外两例。在具有不同突变等位基因分数的多个组织中发现了嵌合现象（MAF，0.03%‐33.03%）。结果表明，嵌合体的MAF可能与表型严重程度有关。这是 AHC 中 ATP1A3 嵌合现象的第一份系统报告，并表明嵌合现象是以前被认为是“从头”AHC 的一个未被识别的来源。识别 ATP1A3 嵌合体为估计复发风险提供了更多证据，并对 AHC 的遗传咨询具有影响。
Alternating hemiplegia of childhood (AHC) is a rare and severe neurodevelopmental disorder characterized by recurrent hemiplegic episodes. Most AHC cases are sporadic and caused by de novo ATP1A3 pathogenic variants. In this study, the aim was to identify the origin of ATP1A3 pathogenic variants in a Chinese cohort. In 105 probands including 101 sporadic and 4 familial cases, 98 patients with ATP1A3 pathogenic variants were identified, and 96.8% were confirmed as de novo. Micro‐droplet digital polymerase chain reaction was applied for detecting ATP1A3 mosaicism in 80 available families. In blood samples, four asymptomatic parents, including two paternal and two maternal, and one proband with a milder phenotype were identified as mosaicism. Six (7.5%) parental mosaicisms were identified in multiple tissues, including four previously identified in blood and two additional cases identified from paternal sperms. Mosaicism was identified in multiple tissues with varied mutant allele fractions (MAFs, 0.03%‐33.03%). The results suggested that MAF of mosaicism may be related to phenotype severity. This is the first systematic report of ATP1A3 mosaicism in AHC and showed mosaicism as an unrecognized source of previously considered “de novo” AHC. Identifying ATP1A3 mosaicism provides more evidence for estimating recurrence risk and has implications in genetic counseling of AHC.
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影响因子：
3.7
作者：
Panagiotakaki E;De Grandis E;Stagnaro M;Heinzen EL;Fons C;Sisodiya S;de Vries B;Goubau C;Weckhuysen S;Kemlink D;Scheffer I;Lesca G;Rabilloud M;Klich A;Ramirez-Camacho A;Ulate-Campos A;Campistol J;Giannotta M;Moutard ML;Doummar D;Hubsch-Bonneaud C;Jaffer F;Cross H;Gurrieri F;Tiziano D;Nevsimalova S;Nicole S;Neville B;van den Maagdenberg AM;Mikati M;Goldstein DB;Vavassori R;Arzimanoglou A;Italian IBAHC Consortium;French AHC Consortium;International AHC Consortium
通讯作者：
International AHC Consortium
影响因子：
3.9
作者：
Xu, Xiaojing;Yang, Xiaoxu;Wu, Qixi;Liu, Aijie;Yang, Xiaoling;Ye, Adam Yongxin;Huang, August Yue;Li, Jiarui;Wang, Meng;Yu, Zhe;Wang, Sheng;Zhang, Zhichao;Wu, Xiru;Wei, Liping;Zhang, Yuehua
通讯作者：
Zhang, Yuehua
iFish：使用基因特异性/家族特异性属性和分类器预测人类非同义变异的致病性
影响因子：
4.6
作者：
Wang Meng;Wei Liping
通讯作者：
Wei Liping
DOI：
10.1126/science.aao4426
发表时间：
2018-02-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lodato MA;Rodin RE;Bohrson CL;Coulter ME;Barton AR;Kwon M;Sherman MA;Vitzthum CM;Luquette LJ;Yandava CN;Yang P;Chittenden TW;Hatem NE;Ryu SC;Woodworth MB;Park PJ;Walsh CA
通讯作者：
Walsh CA
DOI：
10.1073/pnas.1208715109
发表时间：
2012-09-04
影响因子：
11.1
作者：
Schmitt, Michael W.;Kennedy, Scott R.;Loeb, Lawrence A.
通讯作者：
Loeb, Lawrence A.