TY - JOUR
T1 - Prenatal screening for cystic fibrosis
T2 - Past, present and future
AU - Richards, Carolyn S.
AU - Grody, Wayne W.
N1 - Funding Information:
Due to the daunting complexities of the CF gene, the inability of any currently available technology to efficiently detect all possible mutations, as well as concern over the nebulous predictive nature of mutation identification, there ensued a great deal of debate within the genetics community over whether such an imperfect test should be introduced to the public for the purpose of population screening, at least until its utility and impact could be better characterized. To this end, it was recommended that the National Institutes of Health (NIH) fund a series of pilot screening studies to assess the risks and benefits of such a program. The studies were funded through the National Center for Human Genome Research (now the National Human Genome Research Institute) and sponsored by the center’s Ethical, Legal and Social Implications (ELSI) program. Five centers were designated to conduct pilot screening programs on general populations with no family history of CF; at least three additional studies were conducted independently of the NIH consortium. The studies varied in population ethnicity, target size, approach (couple-based vs. sequential screening), type of clinic setting, timing of screening (preconception vs. prenatal) and modes of education, counseling and test reporting. By agreement among the centers, screening was largely focused on the six most prevalent CFTR mutations known at the time. Taken in aggregate, the major lessons learned from the pilot studies were: CF population carrier screening can be delivered efficiently on a large scale without unduly taxing healthcare providers The benefits and risks of CF screening can be conveyed to most patients effectively using a combination of brochures, videos and face-to-face contact with healthcare personnel, but not necessarily requiring certified genetic counselors at all stages of the process There was no significant residual anxiety or depression caused by the screening process, even among positive-negative couples The process could be incorporated into routine clinical settings in a cost-effective manner A number of CF births were prevented in couples who other-wise would never have been alerted to their risk since they had no family history of the disease Interest and uptake in screening was appreciably higher when patients and couples were approached in the prenatal clinical setting as opposed to preconceptionally [9,10]
PY - 2004/1
Y1 - 2004/1
N2 - Prenatal screening for cystic fibrosis is reviewed. The disease, gene involved, molecular basis of disease, genotype/phenotype correlations and pilot trials are discussed, as well as historical perspectives, background and American College of Medical Genetics/American College of Obstetricians and Gynecologists recommendations. A number of complex challenges to the implementation of cystic fibrosis screening exist, including mutation testing of the cystic fibrosis transmembrane conductance regulator gene (CFTR), as well as laboratory and clinical issues. Current technologies for CFTR testing include reverse dot blots, amplification refractory mutation detection systems, oligonucleotide ligation assays, the Invade® assay and NanoChip® system. Emerging technologies are also considered, as well as quality assurance measures including analytical and clinical validation, reporting, residual risk calculations and prenatal diagnosis. An even greater challenge is clinical implementation, which focuses upon education and communication, choosing models, reporting, counseling and prenatal diagnosis.
AB - Prenatal screening for cystic fibrosis is reviewed. The disease, gene involved, molecular basis of disease, genotype/phenotype correlations and pilot trials are discussed, as well as historical perspectives, background and American College of Medical Genetics/American College of Obstetricians and Gynecologists recommendations. A number of complex challenges to the implementation of cystic fibrosis screening exist, including mutation testing of the cystic fibrosis transmembrane conductance regulator gene (CFTR), as well as laboratory and clinical issues. Current technologies for CFTR testing include reverse dot blots, amplification refractory mutation detection systems, oligonucleotide ligation assays, the Invade® assay and NanoChip® system. Emerging technologies are also considered, as well as quality assurance measures including analytical and clinical validation, reporting, residual risk calculations and prenatal diagnosis. An even greater challenge is clinical implementation, which focuses upon education and communication, choosing models, reporting, counseling and prenatal diagnosis.
KW - ASO
KW - ASR
KW - CFTR
KW - Cystic fibrosis
KW - Genetic screening
KW - Microarray
KW - OLA
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U2 - 10.1586/14737159.4.1.49
DO - 10.1586/14737159.4.1.49
M3 - Article
C2 - 14711349
AN - SCOPUS:0347762807
SN - 1473-7159
VL - 4
SP - 49
EP - 62
JO - Expert Review of Molecular Diagnostics
JF - Expert Review of Molecular Diagnostics
IS - 1
ER -