PDF(Pubmed)
Abstract：
Spinocerebellar ataxias (SCAs) are heterogeneous disorders with multiple genetic etiology. Mutations in the GRID2 gene are associated with spinocerebellar ataxia type 18 (SCA-18). We report the first Indian case of SCA-18. The proband is a 7-year-old boy with motor delay, cerebellar signs, and cerebellar atrophy. Whole exome and direct sequencing identified compound heterozygous mutations of the coding and noncoding regions of the GRID2 gene. A literature review of the published cases with pathogenic GRID2 variants was performed. Beside our patients, 32 cases were identified. The majority of reported cases were males, of consanguineous kindreds, with autosomal recessive inheritance. However, a proportion of cases (39%) had autosomal dominant/semidominant inheritance with heterozygous variants. In addition to childhood-onset cerebellar ataxia, other reported features were: early-onset dementia, complicated spastic paraparesis, retinal dystrophy, hearing loss, lower motor neuron signs, and severe global developmental delay in some homozygous cases. Cerebellar atrophy was the commonest neuroimaging finding, with few cases demonstrating brain stem, supratentorial, and white matter abnormalities. Although SCA-18 should be suspected in patients with early-onset cerebellar ataxia, eye movement abnormalities, and motor delay, clinicians should be aware of late-onset, variable presentations with pyramidal signs, dementia, and hearing loss. In suspected cases, if mutations were not detected by whole-exome sequencing, direct sequencing of noncoding regions and chromosomal microarray should be considered.
摘要：
脊髓小脑共济失调（SCAs）是具有多种遗传病因的异质性疾病。GRID2基因的突变与脊髓小脑共济失调18型（SCA-18）有关。我们报告了第一例印度的SCA-18病例。先证者是一个7岁的男孩，有马达延迟，小脑体征,和小脑萎缩.全外显子组和直接测序鉴定了GRID2基因编码区和非编码区的复合杂合突变。对已发表的致病性GRID2变异病例进行了文献综述。除了我们的病人，确定了32例。报告的大多数病例是男性，近亲家族，常染色体隐性遗传。然而,部分病例(39%)具有杂合子变异的常染色体显性/半显性遗传.除了儿童期发病的小脑共济失调,其他报告的特征是：早发性痴呆，复杂的痉挛性轻瘫,视网膜营养不良,听力损失,较低的运动神经元标志，在一些纯合子病例中出现严重的整体发育迟缓。小脑萎缩是最常见的神经影像学发现，很少有病例证明脑干，幕上,和白质异常。尽管SCA-18应该在早发性小脑共济失调患者中被怀疑，眼球运动异常，和电机延迟，临床医生应该意识到迟发性，具有锥体迹象的变量表示，痴呆症,和听力损失。在疑似病例中,如果全外显子组测序没有检测到突变，应考虑非编码区和染色体微阵列的直接测序.
