Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria
Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria
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DOI：
10.1007/s004390051151
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发表时间：
1999-12-01
期刊：
影响因子：
5.3
通讯作者：
Schinzel, A
中科院分区：
文献类型：
--
作者：
Baumer, A;Balmer, D;Schinzel, A
Angelman综合征（AS）是由影响染色体区域15 q12的母体拷贝的遗传异常引起的。直到最近，AS的分子诊断依赖于检测15 q11 -13的缺失、15号染色体的父系单亲二体性（UPD）或印迹突变。第四类遗传缺陷的基础AS最近被描述和UBE 3A基因突变组成。迄今为止报道的绝大多数突变预计会在蛋白质水平上造成重大破坏。目前还不清楚对基因产物影响较小的突变是否会导致较轻形式的AS。本文报告了我们对101例临床诊断的AS患者进行UBE 3A基因突变筛查的结果。非严格的临床标准，故意应用纳入AS患者在这项研究中。通过单链构象多态性（SSCP）和SSCP/限制性片段长度多态性（RFLP）分析进行突变搜索，发现5个新的UBE 3A基因突变以及3个不同的多态性。所有五个突变都在具有AS典型特征的患者中检测到，并且预测在四个病例中引起移码，在第五个病例中引起高度保守残基的取代。我们获得的结果增加了关于UBE 3A基因突变的报道数量有限。从迄今为止的数据中出现的重要方面是，已知作为AS基础的四类遗传缺陷似乎并不涵盖所有病例。大约10%的AS病例（包括一些家族性病例）的遗传缺陷仍然未知。
The Angelman syndrome (AS) is caused by genetic abnormalities affecting the maternal copy of chromosome region 15q12. Until recently, the molecular diagnosis of AS relied on the detection of either a deletion at 15q11-13, a paternal uniparental disomy (UPD) for chromosome 15 or imprinting mutations. A fourth class of genetic defects underlying AS was recently described and consists of mutations of the UBE3A gene. The vast majority of mutations reported so far are predicted to cause major disruptions at the protein level. It is unclear whether mutations with less drastic consequences for the gene product could lead to milder forms of AS. Mie report on our results obtained by screening 101 clinically diagnosed AS patients for mutations in the UBE3A gene. Non-stringent clinical criteria were purposely applied for inclusion of AS patients in this study. The mutation search was carried out by single-strand conformation polymorphism (SSCP), and SSCP/restriction fragment length polymorphism (RFLP) analyses and revealed five novel UBE3A gene mutations as well as three different polymorphisms. All five mutations were detected in patients with typical features of AS and are predicted to cause frameshifts in four cases and the substitution of a highly conserved residue in the fifth. The results we obtained add to the as yet limited number of reports concerning UBE3A gene mutations. Important aspects that emerge from die data available to date is that the four classes of genetic defects known to underlie AS do not appear to cover all cases. The genetic defect underlying approximately 10% of AS cases, including some familial cases, remains unknown.