FBX07-R498X mutation: Phenotypic variability from chorea to early onset parkinsonism within a family
FBX07-R498X mutation: Phenotypic variability from chorea to early onset parkinsonism within a family
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DOI：
10.1016/j.parkreldis.2014.07.016
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发表时间：
2014-11-01
影响因子：
4.1
通讯作者：
Ertan, Sibel
中科院分区：
文献类型：
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作者：
Gunduz, Aysegul;Eken, Asli Gundogdu;Ertan, Sibel
目的：2008年首次报道的FBXO7突变（park15）是早发性帕金森病的单基因原因之一。经典地，park15被认为与先前描述的苍白球锥体综合征相对应。在这里，我们报告了一个独特的库尔德血统家族的临床和遗传发现，该家族具有FBXO7突变，并表现出多种临床表型。方法：该家庭共14人，子女12人，其中3人患病。这三个兄弟姐妹中的两个在我们的诊所接受了检查。对索引病例及其姐姐的DNA样本进行了纯合子定位和外显子组测序。结果：该病例出现进行性语言障碍、严重的冷漠、舞蹈症和抽搐，3年后发展为非常轻微的帕金森病和姿势不稳定。他的妹妹患有年轻时发病的不对称震颤主导型帕金森病，伴有一些非典型特征，如早期发展的姿势不稳定、抽搐和语言失速。她死于一种动刚性条件，并没有发展成舞蹈病。在两例患者中均发现纯合子R498X突变（NM_012179; chr22:31,224,440）。这一结果在两名患者、他们的近亲父母和他们的外祖父的Sanger测序中得到进一步证实；后3个基因为杂合突变（c.C1492T; p.R498X）。结论：这里提出的家族拓宽了帕金森病的临床谱，除了与FBXO7突变有关的帕金森锥体表型外，还包括抽搐和舞蹈病，并指出了家族内表型变异。(C) 2014 Elsevier Ltd.版权所有。
Objective: FBXO7 mutations (PARK 15), first reported in 2008, are among the monogenic causes of early-onset parkinsonism. Classically, PARK 15 was suggested to correspond to previously described pallido-pyramidal syndrome. Here, we report clinical and genetic findings in a unique family of Kurdish origin with an FBXO7 mutation and presenting with diverse clinical phenotypes.Methods: The family consisted of 14 members (12 offspring) of whom three were affected. Two of these three siblings were examined in our clinic. DNA samples from the index case and his elder sister were subjected to homozygosity mapping and exomic sequencing.Results: The index case had progressive speech problems, severe apathy, chorea, and tics at presentation and developed very mild parkinsonism and postural instability after 3 years. His sister had young-onset asymmetric tremor-dominant parkinsonism with some atypical features, such as early development of postural instability, tics, and tachyphemic speech. She died of an akinetic-rigid condition and had not developed chorea. A homozygous R498X mutation was found in both patients (NM_012179; chr22:31,224,440). This result was further confirmed by Sanger sequencing in both patients, their consanguineous parents, and their maternal grandfather; the latter three were found to be heterozygous for the mutation (c.C1492T; p.R498X).Conclusions: The family presented here broadens the clinical spectrum of parkinsonism to include tics and chorea, in addition to the parkinsonian-pyramidal phenotype, in connection with FBXO7 mutations and points to an intrafamilial phenotypic variation. (C) 2014 Elsevier Ltd. All rights reserved.