VAC14 syndrome in two siblings with retinitis pigmentosa and neurodegeneration with brain iron accumulation.
VAC14 syndrome in two siblings with retinitis pigmentosa and neurodegeneration with brain iron accumulation.
复制标题
两兄弟姐妹患有 VAC14 综合征，患有色素性视网膜炎和伴有脑铁积累的神经变性。
DOI：
10.1101/mcs.a003715
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发表时间：
2019
影响因子：
1.8
通讯作者：
Velinov,Milen
中科院分区：
文献类型：
--
作者：
Lyon,GholsonJ;Marchi,Elaine;Ekstein,Joseph;Meiner,Vardiella;Hirsch,Yoel;Scher,Sholem;Yang,Edward;DeVivo,DarrylC;Madrid,Ricardo;Li,Quan;Wang,Kai;Haworth,Andrea;Chilton,Ilana;Chung,WendyK;Velinov,Milen
全外显子组测序用于确定6名儿童早期发病严重进行性痉挛性截瘫和学习障碍的兄弟姐妹中2名出现的快速进展的神经系统疾病的遗传病因。在inVAC14中发现了一个纯合突变（c.2005 5g >T, p, V669L），临床表型与最近描述的vac14相关纹状核变性，儿童期发病综合征（SNDC） （MIM#617054）一致。然而，表型包括视网膜色素变性（RP）的独特临床表现，此前未报道与vac14突变相关。脑磁共振成像（MRI）显示苍白球磁化率异常，可见于神经退行性脑铁积累（NBIA）。RP是一组具有表型/遗传异质性的遗传性视网膜疾病，RP的病理生理基础尚不完全清楚，但被认为是由于原发性视网膜感光细胞退行性过程。大多数RP病例是孤立的（无综合征）；本文报道了两名vac14相关综合征的兄弟姐妹发生RP，建议在未来的研究中探讨RP与vac14相关综合征之间的联系。
Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressing neurological disease present in two of six siblings with early childhood onset of severe progressive spastic paraparesis and learning disabilities. A homozygous mutation (c.2005G>T, p, V669L) was found inVAC14, and the clinical phenotype is consistent with the recently describedVAC14-related striatonigral degeneration, childhood-onset syndrome (SNDC) (MIM#617054). However, the phenotype includes a distinct clinical presentation of retinitis pigmentosa (RP), which has not previously been reported in association withVAC14mutations. Brain magnetic resonance imaging (MRI) revealed abnormal magnetic susceptibility in the globus pallidus, which can be seen in neurodegeneration with brain iron accumulation (NBIA). RP is a group of inherited retinal diseases with phenotypic/genetic heterogeneity, and the pathophysiologic basis of RP is not completely understood but is thought to be due to a primary retinal photoreceptor cell degenerative process. Most cases of RP are seen in isolation (nonsyndromic); this is a report of RP in two siblings withVAC14-associated syndrome, and it is suggested that a connection between RP andVAC14-associated syndrome should be explored in future studies.