Novel compound heterozygous FBXO7 mutations in a family with early onset Parkinson's disease.
Novel compound heterozygous FBXO7 mutations in a family with early onset Parkinson's disease.
复制标题
DOI：
10.1016/j.parkreldis.2020.09.035
复制
发表时间：
2020-11
影响因子：
4.1
通讯作者：
Zabetian CP
中科院分区：
文献类型：
--
作者：
Lorenzo-Betancor O;Lin YH;Samii A;Jayadev S;Kim HM;Longfellow K;Distad BJ;Yearout D;Mata IF;Zabetian CP
F-box蛋白7 （FBXO7）基因突变导致常染色体隐性帕金森病。这通常表现为早发性帕金森锥体综合征，但患者表现出高表型变异性。在这里，我们描述了一个也门家庭的两个新的FBXO7突变的发现。临床数据和DNA可用于三个兄弟姐妹与他们的父母一起患有早发性帕金森病和三个未患病的兄弟姐妹。目标下一代测序小组用于筛选先证者中已知导致帕金森病的14个基因的突变。此外，对SNCA、PARK2、PINK1和PARK7进行拷贝数变异筛选。先证者携带两个新的复合杂合FBXO7突变：外显子1错义突变（p.G39R; c.115G > a）和外显子5移码突变（p.L280fs; c.838del）。突变在家族中与疾病分离，除了一个潜在的症状前个体，其年龄低于其三个受影响兄弟姐妹中的两个的发病年龄。P.G39R发生在一个高度保守的氨基酸残基上，预计这两个突变都是有害的。与大多数报道的家族相反，该家系的表型与临床典型的帕金森病（PD）一致，缺乏锥体体征，对多巴胺能治疗反应良好。我们的研究扩大了与FBXO7相关的表型，包括早发性PD，并扩大了致病突变的列表。这些数据表明，FBXO7应纳入PD的临床基因检测面板，特别是在早期发病或隐性遗传模式的患者中。
Mutations in the F-box protein 7 (FBXO7) gene result in autosomal recessive parkinsonism. This usually manifests as early-onset parkinsonian-pyramidal syndrome but patients exhibit high phenotypic variability. Here we describe the findings of a Yemeni family with two novel FBXO7 mutations. Clinical data and DNA were available for three siblings with early-onset parkinsonism together with their parents and three unaffected siblings. A targeted next generation sequencing panel was used to screen the proband for mutations in 14 genes known to cause a parkinsonian disorder. In addition, SNCA, PARK2, PINK1, and PARK7 were screened for copy number variants. The proband carried two novel compound heterozygous FBXO7 mutations: a missense mutation in exon 1 (p.G39R; c.115G > A) and a frameshift mutation in exon 5 (p.L280fs; c.838del). The mutations segregated with disease in the family with the exception of a potentially pre-symptomatic individual whose age was below the age of onset in two of their three affected siblings. P.G39R occurred at a highly conserved amino acid residue and both mutations were predicted to be deleterious in silico. In contrast to most reported families, the phenotype in this pedigree was consistent with clinically typical Parkinson’s disease (PD) with a lack of pyramidal signs and good response to dopaminergic therapy. Our study expands the phenotype associated with FBXO7 to include early-onset PD and broadens the list of causative mutations. These data suggest that FBXO7 should be included in clinical genetic testing panels for PD, particularly in patients with early onset or a recessive inheritance pattern.
登录
查看更多内容
影响因子：
8.6
作者：
Lohmann, Ebba;Coquel, Anne-Sophie;Brice, Alexis
通讯作者：
Brice, Alexis
影响因子：
4.1
作者：
Cornejo-Olivas, Mario R.;Torres, Luis;Leverenz, James B.
通讯作者：
Leverenz, James B.
影响因子：
4.1
作者：
Gunduz, Aysegul;Eken, Asli Gundogdu;Ertan, Sibel
通讯作者：
Ertan, Sibel
影响因子：
25
作者：
Burchell, Victoria S.;Nelson, David E.;Sanchez-Martinez, Alvaro;Delgado-Camprubi, Marta;Ivatt, Rachael M.;Pogson, Joe H.;Randle, Suzanne J.;Wray, Selina;Lewis, Patrick A.;Houlden, Henry;Abramov, Andrey Y.;Hardy, John;Wood, Nicholas W.;Whitworth, Alexander J.;Laman, Heike;Plun-Favreau, Helene
通讯作者：
Plun-Favreau, Helene
由于 F-Box 唯一蛋白 7 基因中的复合杂合突变，导致青少年发病的帕金森病，伴有锥体征。
影响因子：
4.1
作者：
Wei, Lei;Ding, Li;Long, Ling
通讯作者：
Long, Ling