PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine
PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine
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DOI：
10.1212/wnl.0b013e3182752c46
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发表时间：
2012-11-01
期刊：
影响因子：
9.9
通讯作者：
Szepetowski, Pierre
中科院分区：
文献类型：
--
作者：
Cloarec, Robin;Bruneau, Nadine;Szepetowski, Pierre
目的：最近通过全基因组测序和对 103 个家系的筛查，我们确定了 PRRT2（富含脯氨酸的跨膜蛋白）是导致婴儿惊厥（IC）伴阵发性运动源性运动障碍（PKD）（PKD/IC 综合征，以前称为 ICCA）的基因。存在家族间和家族内的变异性，患者可能患有 IC 或 PKD。 IC 与偏瘫性偏头痛 (HM) 的关联也有报道。为了探索突变和临床谱，我们分析了另外 34 个患有典型 PKD/IC 或伴有偏头痛的 PKD/IC 的家族。方法：我们对先证者及其亲属的所有 PRRT2 编码外显子和外显子-内含子边界进行了桑格测序。结果：在 18 个家族中检测到了 2 个已知的 PRRT2 突变和 2 个新的 PRRT2 突变。在大约 50% 的典型 PKD/IC 中发现了 p.R217Pfs*8 复发突变，而在另一个典型家族中则发现了未报告的 p.R145Gfs*31。 PRRT2 突变也在伴有偏头痛的 PKD/IC 患者中发现：p.R217Pfs*8 与 1 个家族中 HM 相关的 PKD 共分离，并且在 1 例有先兆偏头痛的 IC 患者、相关 PKD/IC 家族的无先兆偏头痛患者以及 1 例 MRI 异常的散发性偏头痛患者中也检测到了 PRRT2 突变。先前报道的 p.R240X 在一名患有无先兆偏头痛的 PKD 患者中被发现。在患有 IC 和先兆偏头痛的 PKD/IC 家族成员中发现了新的移码 p.S248Afs*65。 结论：我们将 PRRT2 突变谱和表型扩展到 HM 和 PKD/IC 背景下的其他类型偏头痛，并强调在 PRRT2 突变患者中观察到的表型多效性。神经病学（R）2012；79：2097-2103
Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine.Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate.Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in approximate to 50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura.Conclusions: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations. Neurology (R) 2012;79:2097-2103