Genetic Diseases
Conditions
Keywords
microarray
Brief summary
The main objective of the multi-centered collaborative study is to evaluate the accuracy, efficacy and clinical advantages of prenatal diagnosis using microarray analysis as compared with conventional karyotyping.
Detailed description
Specifically, the aims are as follows: 1. Demonstrate the performance of microarray analysis as a clinical method for prenatal cytogenetic diagnosis with regard to: 1. Accuracy in the detection of the common autosomal and sex chromosomal aneuploid (trisomies, 13,18,21, 45,X, 47,XXY, etc.) 2. Ability of microarray to diagnose less common, but clinically significant, cytogenetic aneusomies (e.g. DiGeorge, Williams, Smith- Magenis, Prader-Willi syndrome, etc.) currently not detected by conventional karyotype. 3. Evaluation of the utility of microarray in specific clinical scenarios such as ultrasound detection of congenital anomalies and fetal growth disorders. 2. Evaluate the appropriate construction of prenatal diagnostic microarray devices to allow maximal detection of clinically relevant information with minimal detection of unexpected and difficult to interpret findings which have no clinical significance but might provoke patient anxiety. 3. Evaluate the feasibility and cost-effectiveness of using microarrays as a primary prenatal diagnostic tool. 4. Evaluate approaches to integrate microarray into clinical prenatal cytogenetic diagnostic practice. 5. Develop a prenatal diagnostic tissue repository (TDR) to facilitate the further development of microarray technology. This will be used to investigate the molecular etiologies of specific fetal anomalies and to test newer technologies, such as higher resolution microarrays.
Interventions
GENETICMicroarray analysis
Microarray performed on prenatal specimen: Fluorescence in-situ hybridization (FISH) or other standardized tests such as qPCR or MLPA will be performed on the fetal sample to confirm abnormal MA findings of known and unknown clinical significance which are discordant with CC findings, including anomalies normally detected by karyotyping. Microarray analysis of DNA from parental blood samples will be used to determine whether CNVs detected in a fetal sample are also present in a healthy parent, in which case no further evaluation will take place, moreover any finding in a fetus which is duplicated in a parental microarray is considered to be confirmed.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Columbia University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Singleton pregnancy having either chorionic villus sampling in the first trimester or an amniocentesis procedure at or after 16 weeks of gestation performed for prenatal cytogenetic diagnosis 2. Karyotyping to be performed at Genzyme Genetics Cytogenetics Laboratory 3. Trained study personnel available 4. Presenting at pre-specified sites using Genzyme Genetics for routine prenatal diagnostic services
Exclusion criteria
1. Unavailability of one or both biologic parents to provide blood sample (e.g. egg or sperm donor, non-paternity) 2. Patient refusal to allow follow-up through the neonatal period and up to age two if selected 3. Participation in the study in a previous pregnancy 4. Insufficient sample for microarray assay
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Detection rate of fetal cytogentic abnormalites between microarray copy number analysis and karyotype in prenatal samples | Up to 2.5 years after recruitment of 4400 patients. | This is a blinded prospective comparison of microarray copy number analysis to metaphase karyotyping for the detection of common fetal cytogentic abnormalites |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The ability of microarray copy number analysis to identify clinically significant microdeletions and duplications not seen by standard karyotyping | Up to 2.5 years . | This outcome will identify the frequency of clinically significant microdeletions and microduplications that are identified on microarray CNA that were not seen on the clinical karyotype. Only copy number variants over 1 Mb in the backbone and those in predesignated critical regions will be included |
| The rates of clinically significant copy number variants associated with specific prenatal conditions | Up to 2.5 years after recruitment of 4400 patients. | THe frequency of clinically significant copy number variants in cases with fetal anomalies, advanced maternal age, positve serum screening, and fetal growth disorders will be determined. |
Countries
United States
Outcome results
None listed