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

Hereditary Oral Clefts Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00341068
• Other study ID #: 999999053
• Secondary ID: OH99-HG-N053
• Status: Terminated
• Start date: January 1, 2000
• Est. completion date: December 2, 2019

Study information

• Verified date: December 2, 2019
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7451
• Est. completion date: December 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 85 Years

Eligibility

• INCLUSION CRITERIA:

Eligible participants are children and adults with an NTD and their parents residing in the Republic of Ireland, Northern Ireland and the United Kingdom

NTDs are defined to include all forms of spina bifida aperta (meningocele, meningomyelocele), encephalocele, anencephaly, rachischisis, iniencephaly and lipomeningocele. Hydrocephalus, hydranencephaly, dermal sinus and spina bifida occulta do not qualify as NTDs.

For oral clefts, eligible participants are children and adults with a facial cleft in Ireland and their parents.

All families with NTDs or clefts will be recruited for the study.

EXCLUSION CRITERIA:

Those with known syndromes will be excluded or analyzed separately.

Cases for whom both biologic parents are not available will be excluded from some components of triad (case, mother and father) analysis, although the data from the NTD case may be useful for other study components.

Related Conditions & MeSH terms

• Facial Cleft Defect
• Hereditary Oral Clefts
• Neural Tube Defects
• Neural Tube Defects (NTDs)
• Spinal Dysraphism

Locations

Country	Name	City	State
United States	National Human Genome Research Institute (NHGRI), 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Human Genome Research Institute (NHGRI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Develop list of candidate genes for these disorders	Develop list of candidate genes for these disorders	Ongoing
Primary	Identify intronic and coding polymorphisms in candidate genes	Identify intronic and coding polymorphisms in candidate genes	ongoing
Primary	Score collected samples for association and/or linkage between specific alleles and disease status	Score collected samples for association and/or linkage between specific alleles and disease status	ongoing