Abstract：
BACKGROUND: ITPR1 gene encodes inositol 1,4,5-trisphosphate-receptor-type 1, a Ca2+ channel highly expressed in cerebellar Purkinje cells. ITPR1 gene variants, through a loss-of-function mechanism, have been found to be related with the manifestation of spinocerebellar ataxia (SCA) 15, an adult-onset slow progressive cerebellar ataxia, SCA 29, a rare non-progressive congenital cerebellar ataxia and Gillepsie syndrome (SCA 29 phenotype plus aniridia). They share an heterogeneity of additional phenotypic features while no genotype-phenotype correlation has ever been found.
METHODS: Here we report the case of a boy with cerebellar ataxia who came to our clinic due to his cervical dystonia in the form of retrocollis. He presented an early-onset, non-progressive cerebellar ataxia, with cognitive impairment and delayed motor milestones. Whole exome sequencing (WES) revealed an heterozygous nucleotide variation, c.829A > C (p.Ser277Arg) in ITPR1 gene (NM_001168272.1), a de novo ITPR1 variant, as his parents came up with negative genetic testing. Due to his clinical presentation and genetic result, we came up with the diagnosis of SCA 29.
CONCLUSIONS: We described cervical dystonia as a phenotypic feature of ITPR1 related SCA 29, found in a new de novo ITPR1-variant.
METHODS: Here we report the case of a boy with cerebellar ataxia who came to our clinic due to his cervical dystonia in the form of retrocollis. He presented an early-onset, non-progressive cerebellar ataxia, with cognitive impairment and delayed motor milestones. Whole exome sequencing (WES) revealed an heterozygous nucleotide variation, c.829A > C (p.Ser277Arg) in ITPR1 gene (NM_001168272.1), a de novo ITPR1 variant, as his parents came up with negative genetic testing. Due to his clinical presentation and genetic result, we came up with the diagnosis of SCA 29.
CONCLUSIONS: We described cervical dystonia as a phenotypic feature of ITPR1 related SCA 29, found in a new de novo ITPR1-variant.
摘要：
背景：ITPR1基因编码肌醇1,4,5-三磷酸受体1型，一种在小脑浦肯野细胞中高度表达的Ca2+通道。ITPR1基因变异,通过功能丧失机制，已发现与脊髓小脑共济失调（SCA）15的表现有关，这是一种成人发作的缓慢进行性小脑共济失调，SCA29，一种罕见的非进行性先天性小脑共济失调和Gillepsie综合征（SCA29表型加无虹膜）。它们具有其他表型特征的异质性，而从未发现基因型-表型相关性。
方法：在这里，我们报告了一个小脑性共济失调的男孩，由于他的颈肌张力障碍以逆行形式来到我们的诊所。他提出了一个早期发作，非进行性小脑共济失调,认知障碍和运动里程碑延迟。全外显子组测序（WES）揭示了一个杂合的核苷酸变异，c.829A>C（p.Ser277Arg)在ITPR1基因(NM_001168272.1)中,从头ITPR1变体，因为他的父母提出了阴性基因检测。由于他的临床表现和遗传结果，我们得出了SCA29的诊断。
结论：我们将宫颈肌张力障碍描述为ITPR1相关SCA29的表型特征，发现于一个新的从头ITPR1变体中。
方法：在这里，我们报告了一个小脑性共济失调的男孩，由于他的颈肌张力障碍以逆行形式来到我们的诊所。他提出了一个早期发作，非进行性小脑共济失调,认知障碍和运动里程碑延迟。全外显子组测序（WES）揭示了一个杂合的核苷酸变异，c.829A>C（p.Ser277Arg)在ITPR1基因(NM_001168272.1)中,从头ITPR1变体，因为他的父母提出了阴性基因检测。由于他的临床表现和遗传结果，我们得出了SCA29的诊断。
结论：我们将宫颈肌张力障碍描述为ITPR1相关SCA29的表型特征，发现于一个新的从头ITPR1变体中。
