公开(公告)号：WO1998001740A2

公开(公告)日：1998-01-15

申请号：PCT/US1997011687

申请日：1997-07-07

Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION

Inventor： UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  KEATING, Mark, T. ,  MORRIS, Colleen, A.

IPC: G01N00/00

CPC classification number: A61K31/00 ,  A61B17/22 ,  C07K14/78 ,  C12Q1/6827 ,  C12Q1/6841 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158

Abstract: Williams syndrome (WS) is a developmental disorder that includes poor visuospatial constructive cognition. This syndrome has been studied to identify genes important for human cognitive development. Two families are described which have a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest (63.6 kb) deletion revealed two genes, elastin (ELN) and LIM-kinase 1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in impaired visuospatial constructive cognition.

Abstract translation: 威廉姆斯综合征（WS）是一种发育障碍，包括差的视觉空间建构认知。 已经研究了该综合征，以鉴定对人类认知发育至关重要的基因。 描述了具有部分WS表型的两个家族; 受影响的成员具有特定的WS认知特征和血管疾病，但缺乏其他WS特征。 亚型显示染色体7q11.23缺失与这两种家族中的这种表型相似。 受最小（63.6kb）缺失影响的区域的DNA序列分析显示两个基因，弹性蛋白（ELN）和LIM-激酶1（LIMK1）。 后者编码具有LIM结构域的新型蛋白激酶，并在脑中强烈表达。 因为ELN突变导致血管疾病而不是认知异常，所以这些数据暗示了LIMK1半透明度受损的视空间建设性认知。

公开(公告)号：WO1994023638A3

公开(公告)日：1994-10-27

申请号：PCT/US1994003426

申请日：1994-04-04

Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  UNIVERSITY AND COMMUNITY COLLEGE SYSTEM OF NEVADA

Inventor： UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  UNIVERSITY AND COMMUNITY COLLEGE SYSTEM OF NEVADA ,  KEATING, Mark, T. ,  LEPPERT, Mark, F. ,  MORRIS, Colleen, A.

IPC: C12Q01/68

公开(公告)号：EP0694080B1

公开(公告)日：2005-12-07

申请号：EP94913974.5

申请日：1994-04-04

Applicant: University of Utah Research Foundation ,  UNIVERSITY AND COMMUNITY COLLEGE SYSTEM OF NEVADA

Inventor： KEATING, Mark, T. ,  LEPPERT, Mark, F. ,  MORRIS, Colleen, A.

IPC: C12Q1/68 ,  C12P19/34 ,  C12N1/08 ,  C07H17/00

CPC classification number: C12Q1/6883 ,  A61B17/22 ,  A61K31/00 ,  C07K14/78 ,  C12Q1/6841 ,  C12Q2600/156 ,  C12Q2600/172 ,  Y10S435/968 ,  Y10T436/143333

Abstract: The invention relates to the identification of the molecular basis of supravalvular aortic stenosis (SVAS) and Williams syndrome. More specifically, the invention has identified that elastin causes or is involved in the pathogenesis of SVAS and Williams syndrome. Molecular variants of the elastin gene contribute to SVAS and Williams syndrome. The analysis of the elastin gene will provide an early diagnosis of subjects with SVAS and Williams syndrome. The diagnostic method comprises analyzing the DNA sequence of the elastin gene of an individual to be tested and comparing it with the DNA sequence of the native, non-variant elastin gene. In a second embodiment, the elastin gene of an individual to be tested is screened for mutations associated with SVAS or Williams syndrome. Presymptomatic diagnosis of SVAS and Williams syndrome will enable practitioners to prevent vascular obstruction using existing medical therapies like beta adrenergic blocking agents.

公开(公告)号：EP1019714B1

公开(公告)日：2009-03-18

申请号：EP97936952.7

申请日：1997-07-07

Applicant: University of Utah Research Foundation ,  UNIVERSITY AND COMMUNITY COLLEGE SYSTEM OF NEVADA

Inventor： KEATING, Mark, T. ,  MORRIS, Colleen, A.

IPC: G01N33/00

CPC classification number: A61K31/00 ,  A61B17/22 ,  C07K14/78 ,  C12Q1/6827 ,  C12Q1/6841 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158

Abstract: Williams syndrome (WS) is a developmental disorder that includes poor visuospatial constructive cognition. This syndrome has been studied to identify genes important for human cognitive development. Two families are described which have a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest (63.6 kb) deletion revealed two genes, elastin (ELN) and LIM-kinase 1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in impaired visuospatial constructive cognition.

公开(公告)号：EP1019714A2

公开(公告)日：2000-07-19

申请号：EP97936952.7

申请日：1997-07-07

Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  UNIVERSITY AND COMMUNITY COLLEGE SYSTEM OF NEVADA

Inventor： KEATING, Mark, T. ,  MORRIS, Colleen, A.

IPC: G01N33/00

CPC classification number: A61K31/00 ,  A61B17/22 ,  C07K14/78 ,  C12Q1/6827 ,  C12Q1/6841 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158

Abstract: Williams syndrome (WS) is a developmental disorder that includes poor visuospatial constructive cognition. This syndrome has been studied to identify genes important for human cognitive development. Two families are described which have a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest (63.6 kb) deletion revealed two genes, elastin (ELN) and LIM-kinase 1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in impaired visuospatial constructive cognition.

公开(公告)号：EP0694080A1

公开(公告)日：1996-01-31

申请号：EP94913974.0

申请日：1994-04-04

Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  UNIVERSITY AND COMMUNITY COLLEGE SYSTEM OF NEVADA

Inventor： KEATING, Mark, T. ,  LEPPERT, Mark, F. ,  MORRIS, Colleen, A.

IPC: G01N33 ,  A61K31 ,  C07K14 ,  C12N15 ,  C12Q1 ,  A61B17

CPC classification number: C12Q1/6883 ,  A61B17/22 ,  A61K31/00 ,  C07K14/78 ,  C12Q1/6841 ,  C12Q2600/156 ,  C12Q2600/172 ,  Y10S435/968 ,  Y10T436/143333

Abstract: The invention relates to the identification of the molecular basis of supravalvular aortic stenosis (SVAS) and Williams syndrome. More specifically, the invention has identified that elastin causes or is involved in the pathogenesis of SVAS and Williams syndrome. Molecular variants of the elastin gene contribute to SVAS and Williams syndrome. The analysis of the elastin gene will provide an early diagnosis of subjects with SVAS and Williams syndrome. The diagnostic method comprises analyzing the DNA sequence of the elastin gene of an individual to be tested and comparing it with the DNA sequence of the native, non-variant elastin gene. In a second embodiment, the elastin gene of an individual to be tested is screened for mutations associated with SVAS or Williams syndrome. Presymptomatic diagnosis of SVAS and Williams syndrome will enable practitioners to prevent vascular obstruction using existing medical therapies like beta adrenergic blocking agents.