Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005322
Status:
COMPLETED
Last Update Posted:
2016-09-28
First Post:
2000-05-25
Brief Title:
Molecular Genetic Epidemiology of Endocardial Cushion Defects - SCOR in Pediatric Cardiovascular Disease
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2004-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To identify genes involved in the pathogenesis of congenital heart disease including atrial septal defects ASDs paramembranous ventricular septal defects VSDs and atrioventricular canal defects AVCDs
Detailed Description:
BACKGROUND
In 1987 when the third renewal of the Ischemic Heart Disease Specialized Centers of Research renewal was considered the Cardiology Advisory Committee recommended that the scope of the SCORs should be broadened to include peripheral vascular disease congenital heart disease and heart failure The National Heart Lung and Blood Advisory Council concurred in this recommendation and the Request for Applications for a Specialized Centers of Research in Coronary and Vascular Disease Heart Failure and Congenital Heart Disease was issued in July 1987 The study was renewed in 1999 as P50HL62178
DESIGN NARRATIVE
Beginning in 1990 the molecular genetic epidemiology of endocardial cushion defects in four groups of individuals was investigated in this subproject within a SCOR in Pediatric Cardiovascular Disease Subjects included those with Down syndrome and endocardial cushion defects those with non-syndromic endocardial cushion defects those with Down syndrome and no congenital heart disease and those with normal hearts Examinations were carried out in the relatives of these subjects to ascertain whether they had endocardial cushion defects and other chromosome 21-related disorders such as Down syndrome and Alzheimers disease This was accomplished by obtaining family pedigrees and examining 1st 2nd and 3rd degree relatives utilizing electrocardiographic and echocardiographic techniques Venous blood was obtained from the probands and the relatives for association studies with DNA probes that were known to relate to chromosome 21 and to genes located on other chromosomes that may affect cardiac embryogenesis Segregation analysis focused on families of the subjects with non-syndromic endocardial cushion defects to determine whether there was evidence for a major gene defect which resulted in deformities of the atrioventricular canal If and when such evidence was found linkage studies were carried out in an attempt to pinpoint the location of the major gene in the genome
When the SCOR was renewed in 1995 the objectives were to identify polymorphisms in candidate genes and to use the polymorphisms for genetic association studies in patients Subjects included those with Down syndrome and atrioventricular canal defects non-Down subjects with atrioventricular canal defects Down syndrome subjects with no functional heart disease normal subjects with no heart disease or Down syndrome Down syndrome subjects with perimembranous interventricular septal defects and non-Down subjects with perimembranous interventricular septal defects In addition polymorphisms within candidate genes as well as the highly polymorphic short tandem repeat polymorphisms STRPs were used in a genome-wide linkage search for the gene in large families with multiple affected individuals When association or linkage studies suggested involvement of a specific gene a search for mutations in the gene was carried out In addition the investigators determined whether a likely candidate chromosomal region chromosome 21q211-qter was involved in non-Downs AVCD by using molecular techniques to search for allele loss uniparental disomy and cryptic translocations They also investigated the molecular genetic variability associated with endocardial cushion and ventricular septal development in Down syndrome subjects with and without heart disease and in normal subjects Examinations were carried out in the relatives of these subjects to ascertain whether they had congenital heart defects or any other congenital anomalies This was accomplished by obtaining family pedigrees medical histories and examining 1st degree relatives and if positive 2nd and 3rd degree relatives utilizing echocardiographic and electrocardiographic techniques
The study completion date listed in this record was obtained from the Completed Date entered in the Query View Report System QVR
In 1987 when the third renewal of the Ischemic Heart Disease Specialized Centers of Research renewal was considered the Cardiology Advisory Committee recommended that the scope of the SCORs should be broadened to include peripheral vascular disease congenital heart disease and heart failure The National Heart Lung and Blood Advisory Council concurred in this recommendation and the Request for Applications for a Specialized Centers of Research in Coronary and Vascular Disease Heart Failure and Congenital Heart Disease was issued in July 1987 The study was renewed in 1999 as P50HL62178
DESIGN NARRATIVE
Beginning in 1990 the molecular genetic epidemiology of endocardial cushion defects in four groups of individuals was investigated in this subproject within a SCOR in Pediatric Cardiovascular Disease Subjects included those with Down syndrome and endocardial cushion defects those with non-syndromic endocardial cushion defects those with Down syndrome and no congenital heart disease and those with normal hearts Examinations were carried out in the relatives of these subjects to ascertain whether they had endocardial cushion defects and other chromosome 21-related disorders such as Down syndrome and Alzheimers disease This was accomplished by obtaining family pedigrees and examining 1st 2nd and 3rd degree relatives utilizing electrocardiographic and echocardiographic techniques Venous blood was obtained from the probands and the relatives for association studies with DNA probes that were known to relate to chromosome 21 and to genes located on other chromosomes that may affect cardiac embryogenesis Segregation analysis focused on families of the subjects with non-syndromic endocardial cushion defects to determine whether there was evidence for a major gene defect which resulted in deformities of the atrioventricular canal If and when such evidence was found linkage studies were carried out in an attempt to pinpoint the location of the major gene in the genome
When the SCOR was renewed in 1995 the objectives were to identify polymorphisms in candidate genes and to use the polymorphisms for genetic association studies in patients Subjects included those with Down syndrome and atrioventricular canal defects non-Down subjects with atrioventricular canal defects Down syndrome subjects with no functional heart disease normal subjects with no heart disease or Down syndrome Down syndrome subjects with perimembranous interventricular septal defects and non-Down subjects with perimembranous interventricular septal defects In addition polymorphisms within candidate genes as well as the highly polymorphic short tandem repeat polymorphisms STRPs were used in a genome-wide linkage search for the gene in large families with multiple affected individuals When association or linkage studies suggested involvement of a specific gene a search for mutations in the gene was carried out In addition the investigators determined whether a likely candidate chromosomal region chromosome 21q211-qter was involved in non-Downs AVCD by using molecular techniques to search for allele loss uniparental disomy and cryptic translocations They also investigated the molecular genetic variability associated with endocardial cushion and ventricular septal development in Down syndrome subjects with and without heart disease and in normal subjects Examinations were carried out in the relatives of these subjects to ascertain whether they had congenital heart defects or any other congenital anomalies This was accomplished by obtaining family pedigrees medical histories and examining 1st degree relatives and if positive 2nd and 3rd degree relatives utilizing echocardiographic and electrocardiographic techniques
The study completion date listed in this record was obtained from the Completed Date entered in the Query View Report System QVR
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P50HL042266 | NIH | None | httpsreporternihgovquickSearchP50HL042266 |