INTRODUCTION Biallelic mutations in STUB1, which encodes the E3 ubiquitin ligase CHIP, were originally described in association with SCAR16, a rare autosomal recessive spinocerebellar ataxia, so far reported in 16 kindreds. In the last 2 years, a new form of spinocerebellar ataxia (SCA48), associated with heterozygous mutations in the same gene, has been described in 12 kindreds with autosomal dominant inheritance. METHODS We reviewed molecular and clinical findings of both SCAR16 and SCA48 described patients. RESULTS AND CONCLUSION SCAR16 is characterized by early onset spastic ataxia and a wide disease spectrum, including cognitive dysfunction, hyperkinetic disorders, epilepsy, peripheral neuropathy, and hypogonadism. SCA48 is an adult-onset syndrome characterized by ataxia and cognitive-psychiatric features, variably associated with chorea, parkinsonism, dystonia, and urinary symptoms. SCA48, the last dominant ataxia to be described, could emerge as the most frequent among the SCAs due to conventional mutations. The overlap of several clinical signs between SCAR16 and SCA48 indicates the presence of a continuous clinical spectrum among recessively and dominantly inherited mutations of STUB1. Different kinds of mutations, scattered over the three gene domains, have been found in both disorders. Their pathogenesis and the relationship between SCA48 and SCAR16 remain to be clarified.

中文翻译：

---

脊髓小脑共济失调48型：最后但并非最不重要。

引言STUB1中的双等位基因突变最初编码为E3泛素连接酶CHIP，与SCAR16有关，SCAR16是一种罕见的常染色体隐性隐性脊髓小脑共济失调，迄今已有16种人报道。在过去的两年中，已经在12个具有常染色体显性遗传的亲戚中描述了一种新形式的脊髓小脑性共济失调（SCA48），与同一基因的杂合突变相关。方法我们回顾了SCAR16和SCA48所述患者的分子和临床发现。结果与结论SCAR16的特征是早期发作性痉挛性共济失调和广泛的疾病谱，包括认知功能障碍，运动过度障碍，癫痫，周围神经病和性腺功能减退。SCA48是一种成人发病综合​​征，其特征是共济失调和认知心理特征，并与舞蹈病，帕金森症，肌张力障碍和泌尿系统症状。SCA48是最后描述的主要共济失调，由于常规突变，它可能成为SCA中最常见的共济失调。SCAR16和SCA48之间的几种临床体征重叠表明，在STUB1的隐性和显性遗传突变中存在连续的临床谱图。在这两种疾病中都发现了分布在三个基因域上的不同种类的突变。它们的发病机制以及SCA48和SCAR16之间的关系仍有待阐明。SCAR16和SCA48之间的几种临床体征重叠表明，在STUB1的隐性和显性遗传突变中存在连续的临床谱图。在这两种疾病中都发现了分布在三个基因域上的不同种类的突变。它们的发病机制以及SCA48和SCAR16之间的关系仍有待阐明。SCAR16和SCA48之间的几种临床体征重叠表明，在STUB1的隐性和显性遗传突变中存在连续的临床谱图。在这两种疾病中都发现了分布在三个基因域上的不同种类的突变。它们的发病机制以及SCA48和SCAR16之间的关系仍有待阐明。