Genetic Analysis of Neural Tube and Orofacial Cleft Defects in the Irish Population

Terminated

• Conditions: Hereditary Oral Clefts; Neural Tube Defects (NTDs); Facial Cleft Defect

• Registration Number: NCT00341068
• Lead Sponsor: National Human Genome Research Institute (NHGRI)

Brief Summary

In a collaborative effort with the Health Research Board, the national organization for medical research in the Republic of Ireland, individuals with neural tube defects (NTDs) or facial cleft defects and their parents will be studied. With the exception of a few well-described syndromes most cases of NTDs and facial clefts are not inherited in a Mendelian fashion. Nearly all incident cases occur in families with no prior history of the defects. The observed recurrence risk in families with an NTD child is 10-12 fold higher than the general population suggesting that inherited factors modify this risk. Historically, the incidence of NTDs in Ireland was 5-8 fold higher than the USA. The aim of this study is to identify the gene(s) involved in these defects using standard genetic epidemiology approaches, transmission disequilibrium testing and gene mapping strategies. We will initially evaluate genes known to be involved in folate metabolism and pattern formation (development of the body). The major outcomes measured will be aggregate allele frequencies in case groups compared to controls. Biochemical parameters in red cells and plasma will also be measured. Comparisons will be made between the presence of genetics variants, biochemical parameters and clinical phenotype. Characterizing the genes associated with these defects should provide insight into the etiology and metabolic processes that may be involved, furthering prevention and intervention efforts.

Detailed Description

In a collaborative effort with the Health Research Board, the national organization for medical research in the Republic of Ireland, individuals with neural tube defects (NTDs) or facial cleft defects and their parents will be studied. With the exception of a few well-described syndromes most cases of NTDs and facial clefts are not inherited in a Mendelian fashion. Nearly all incident cases occur in families with no prior history of the defects. However, the observed recurrence risk in families with an NTD child is 10-20 fold higher than the general population incidence suggesting that inherited factors modify this risk. Historically, the incidence of NTDs in Ireland was 5-8 fold higher than the USA. The aim of this study is to identify the gene(s) involved in these defects using standard genetic epidemiology approaches, transmission disequilibrium testing and gene mapping strategies. We will initially evaluate genes known to be involved in folate metabolism and pattern formation (development of the body). The major outcomes measured will be aggregate allele frequencies in case groups compared to controls. Biochemical parameters in red blood cells and plasma will also be measured. Comparisons will be made between the presence of genetics variants, biochemical parameters and clinical phenotype. Characterizing the genes associated with these defects should provide insight into the etiology and metabolic processes that may be involved, furthering prevention and intervention efforts.

Study Timeline

• Study Start: 2000-01-01
• Study First Submitted: 2006-06-19
• Study First Submitted QC: 2006-06-19
• Study First Posted: 2006-06-21
• Status Verified: 2019-12-02
• Study Completion: 2019-12-02
• Last Update Submitted: 2019-12-04
• Last Update Posted: 2019-12-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7451

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Identify intronic and coding polymorphisms in candidate genes	ongoing	Identify intronic and coding polymorphisms in candidate genes
Develop list of candidate genes for these disorders	Ongoing	Develop list of candidate genes for these disorders
Score collected samples for association and/or linkage between specific alleles and disease status	ongoing	Score collected samples for association and/or linkage between specific alleles and disease status

Trial Locations

Locations (1)

National Human Genome Research Institute (NHGRI), 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States