公开(公告)号：US07208270B2

公开(公告)日：2007-04-24

申请号：US10176372

申请日：2002-06-21

申请人： Burkhard Jansen ,  Trevor Lucas

发明人： Burkhard Jansen ,  Trevor Lucas

IPC分类号： C12Q1/68 ,  G01N33/53 ,  C12P19/34

CPC分类号： G01N33/6896 ,  A01K2217/05 ,  A61K38/1709 ,  C07K1/22 ,  C07K14/47 ,  C07K14/4713 ,  C07K16/18 ,  C12Q1/6883 ,  C12Q2600/156 ,  G01N33/564 ,  G01N33/57484 ,  G01N33/6893 ,  G01N2800/285

摘要： Described is a method for diagnosing a person having multiple sclerosis (MS) or being at risk of developing MS, comprising the following steps: providing a sample of a body fluid or tissue from said person, said sample containing at least one of the wild type SCF-Apoptosis-Response Gene- (wt-SARG-1-) protein and nucleic acids encoding wt-SARG-1, if taken from a person not having MS or a risk of aquiring MS, detecting the presence of wt-SARG-1-protein or nucleic acids encoding wt-SARG-1 in said sample and diagnosing MS or a risk of aquiring MS, if wt-SARG-1-protein or nucleic acids encoding wt-SARG-1 are not present in said sample.

摘要翻译： 描述了用于诊断具有多发性硬化症（MS）或处于发展MS风险中的人的方法，包括以下步骤：从所述人提供体液或组织的样品，所述样品含有至少一种野生型 SCF-细胞凋亡 - 应答基因 - （wt-SARG-1-）蛋白和编码wt-SARG-1的核酸，如果取自不具有MS或没有MS的风险的人，则检测wt-SARG-1的存在 - 如果wt-SARG-1蛋白或编码wt-SARG-1的核酸不存在于所述样品中，则在所述样品中编码wt-SARG-1的蛋白质或核酸，并诊断MS或获得MS的风险。

公开(公告)号：US08119344B2

公开(公告)日：2012-02-21

申请号：US12389134

申请日：2009-02-19

申请人： Trevor Lucas ,  Klemens Frei ,  Wolf-Dieter Baumgartner

发明人： Trevor Lucas ,  Klemens Frei ,  Wolf-Dieter Baumgartner

IPC分类号： C12Q1/68 ,  C12P19/34

CPC分类号： C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/16

摘要： Homozygous alterations in the gap junction protein GJB2 (connexin 26), within the DFNB1 locus, are responsible for up to 50% of autosomal recessive non-syndromic hearing impairment (NSHI). Analysis of the GJB2 promoter revealed the potential importance of T-228C in the regulation of GJB2 expression. Of regulatory factors known to be expressed in the inner ear, the T-228C transition would delete potential binding sites for the X-box binding protein (RFX1) and the H6 homeobox 3 (HMX3/Nk×5.1) transcription factor which has been linked to hearing impairment. These results suggest that T-228C may represent the most common mutation associated with development of NSHI in Caucasian populations identified to date and should be included in worldwide newborn screening programs for NSHI.

摘要翻译： 在DFNB1基因座内的间隙连接蛋白GJB2（连接蛋白26）中的纯合改变负责高达常染色体隐性非综合征性听觉障碍（NSHI）的50％。 GJB2启动子的分析揭示了T-228C在调控GJB2表达中的潜在重要性。 已知在内耳中表达的调节因子，T-228C转换将删除X-box结合蛋白（RFX1）和已连接的H6同源盒3（HMX3 / Nk×5.1）转录因子的潜在结合位点 听力障碍。 这些结果表明，T-228C可能代表了迄今为止确定的白种人群体中与NSHI的发展相关的最常见突变，并应被纳入全球新生儿NSHI新生儿筛查计划。

公开(公告)号：US20090226920A1

公开(公告)日：2009-09-10

申请号：US12389134

申请日：2009-02-19

申请人： Trevor Lucas ,  Klemens Frei ,  Wolf-Dieter Baumgartner

发明人： Trevor Lucas ,  Klemens Frei ,  Wolf-Dieter Baumgartner

IPC分类号： C12Q1/68 ,  C07H21/04

CPC分类号： C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/16

摘要： Homozygous alterations in the gap junction protein GJB2 (connexin 26), within the DFNB1 locus, are responsible for up to 50% of autosomal recessive non-syndromic hearing impairment (NSHI). Mutations have been described throughout the coding region and more rarely, within the splice donor site. To further investigate the role of GJB2 in NSHI, we have now screened the putative 5′ regulatory region for novel alterations. In idiopathic cases of NSHI lacking known pathogenic alterations in GJB2, we have now identified a T→C transition 228 bp proximal to the transcriptional start site (T-228C) present at a homozygous frequency of 0.2, which is significantly overrepresented in comparison to the predicted homozygous allele frequencies in the healthy population (0.0144). In a NSHI family, inheritance of T-228C was shown to segregate on independent chromosomes with HI in conjunction with heterozygous inheritance of 35 delG, the most common Caucasian mutation in the GJB2 coding region. In a patient group bearing heterozygous pathogenic mutations, homozygousity for T-228C was also highly overrepresented (0.267) and not exclusively linked to the 35delG mutation in cis. However, in all cases of NSHI examined, 35delG homozygousity was linked to T-228C in cis. Analysis of the GJB2 promoter revealed the potential importance of T-228C in the regulation of GJB2 expression. Of regulatory factors known to be expressed in the inner ear, the T-228C transition would delete potential binding sites for the X-box binding protein (RFX1) and the H6 homeobox 3 (HMX3/Nk×5.1) transcription factor which has been linked to hearing impairment. These results suggest that T-228C may represent the most common mutation associated with development of NSHI in Caucasian populations identified to date and should be included in worldwide newborn screening programs for NSHI.

摘要翻译： 在DFNB1基因座内的间隙连接蛋白GJB2（连接蛋白26）中的纯合改变负责高达常染色体隐性非综合征性听觉障碍（NSHI）的50％。 已经在整个编码区中描述了突变，更罕见的是在剪接供体位点内。 为了进一步研究GJB2在NSHI中的作用，我们现在已经筛选了推定的5'调控区域进行新的改变。 在NSJ的特发性病例中，在GJB2中缺乏已知的致病性改变，我们现在已经确定了以纯合子频率为0.2存在的转录起始位点（T-228C）近端228b的T> C转换，其显着超过 健康人群中预测的纯合等位基因频率（0.0144）。 在NSHI家族中，T-228C的遗传被证明在具有HI的独立染色体上与35deG的杂合遗传（GJB2编码区中最常见的白种人突变）分离。 在带有杂合性致病突变的患者组中，T-228C的纯合性也高度过度表达（0.267），而不是与顺式的35delG突变完全相关。 然而，在所有检查NSHI的情况下，35delG纯合与T-228C连接。 GJB2启动子的分析揭示了T-228C在调控GJB2表达中的潜在重要性。 已知在内耳中表达的调节因子，T-228C转换将删除已连接的X盒结合蛋白（RFX1）和H6同源盒3（HMX3 / Nkx5.1）转录因子的潜在结合位点 听力障碍。 这些结果表明，T-228C可能代表了迄今为止确定的白种人群体中与NSHI的发展相关的最常见的突变，应该被纳入全球NSHI的新生儿筛查计划。