ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia.
ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia.
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DOI：
10.1007/s10048-008-0131-7
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发表时间：
2008-07
期刊：
影响因子：
2.2
通讯作者：
Kremer, Berry
中科院分区：
文献类型：
--
作者：
Vermeer, Sascha;Meijer, Rowdy P. P.;Pijl, Benjamin J.;Timmermans, Janneke;Cruysberg, Johannes R. M.;Bos, Maaike M.;Schelhaas, Helenius J.;van de Warrenburg, Bart P. C.;Knoers, Nine V. A. M.;Scheffer, Hans;Kremer, Berry
Charlevoix-Saguenay的常染色体隐性遗传痉挛性共济失调（ARSACS：MIM 270550）是一种神经退行性疾病，其特征是早发性小脑共济失调伴痉挛和周围神经病变。这种疾病被认为是罕见的，最早是在七十年代末在魁北克孤立的Charlevoix-Saguenay地区的法裔加拿大人中描述的。如今，人们知道，这种疾病不仅限于本地区，而且在世界范围内发生。我们的目的是通过测序完整的SACS基因来确定荷兰隐性早发性小脑性共济失调患者中的常染色体隐性痉挛性共济失调病例。在荷兰的一个队列中，43名25岁以前发病的共济失调患者中，我们确定了16名SACS基因突变的患者（共23名患者）。其中9例为纯合突变，7例为复合杂合突变。回顾过去，携带突变的患者的表型非常一致：小脑共济失调在13岁之前发病，下肢痉挛和感觉运动轴索神经病，以及小脑（蚓部）萎缩的磁共振成像，与先前描述的核心ARSACS表型一致。在这组荷兰患者中发现的高突变率（37%）表明ARSACS比以前估计的要频繁得多。我们预测，SACS突变分析的可用性以及对ARSACS表型特征的认识的提高将导致许多额外患者的诊断，甚至可能在更年轻的年龄。
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS: MIM 270550) is a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. This disorder, considered to be rare, was first described in the late seventies among French Canadians in the isolated Charlevoix-Saguenay region of Quebec. Nowadays, it is known that the disorder is not only limited to this region but occurs worldwide. Our objective was to identify cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) in Dutch patients with recessive early-onset cerebellar ataxia by sequencing the complete SACS gene. In a Dutch cohort of 43 index patients with ataxia onset before age 25, we identified 16 index patients (total 23 patients) with mutations in the SACS gene. Nine of them had homozygous mutations, and seven of them had compound heterozygous mutations. Retrospectively, the phenotype of patients carrying mutations was remarkably uniform: cerebellar ataxia with onset before age 13 years, lower limb spasticity and sensorimotor axonal neuropathy, and cerebellar (vermis) atrophy on magnetic resonance imaging, consistent with the core ARSACS phenotype previously described. The high rate of mutations (37%) identified in this cohort of Dutch patients suggests that ARSACS is substantially more frequent than previously estimated. We predict that the availability of SACS mutation analysis as well as an increasing awareness of the characteristic ARSACS phenotype will lead to the diagnosis of many additional patients, possibly even at a younger age.
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影响因子：
14.5
作者：
Klebe, Stephan;Azzedine, Hamid;Stevanin, Giovanni
通讯作者：
Stevanin, Giovanni
影响因子：
4.4
作者：
Shimazaki, Haruo;Sakoe, Kumi;Takiyama, Yoshihisa
通讯作者：
Takiyama, Yoshihisa
影响因子：
--
作者：
El Euch-Fayache, G;Lalani, I;Hentati, F
通讯作者：
Hentati, F
影响因子：
3
作者：
BOUCHARD, JP;BARBEAU, A;BOUCHARD, RW
通讯作者：
BOUCHARD, RW
影响因子：
14.5
作者：
Le Ber, I;Bouslam, N;Dürr, A
通讯作者：
Dürr, A