Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel

Watson, Michael S.; Cutting, Garry R.; Desnick, Robert J.; Driscoll, Deborah A.; Klinger, Katherine W.; Mennuti, Michael T.; Palomaki, Glenn E.; Popovich, Bradley W.; Pratt, Victoria M.; Rohlfs, Elizabeth M.; Strom, Charles M.; Richards, C. Sue; Witt, David R.; Grody, Wayne W.

doi:10.1097/01.gim.0000139506.11694.7c

Cited by 419 publications

(361 citation statements)

References 8 publications

Supporting

Mentioning

350

Contrasting

Unclassified

Order By: Relevance

“…It may be noted that the 1078delT was recently removed from the core mutation screening panel because of its rarity. 9 Our original homologous recombination strategy, modeled on the methodology used to create gene knockouts in mice, called for the design of two targeting arms for each mutation site of interest: a long arm, 4 to 6 kb in size, and a short arm, 2 to 4 kb in size. These targeting arms, contiguous in sequence, were polymerase chain reaction (PCR) amplified from human bacterial artificial chromosome (BAC) DNA (ResGen, Birmingham, AL) containing the CFTR gene.…”

Section: Sample Construction and Preparationmentioning

confidence: 99%

A Novel Method for Creating Artificial Mutant Samples for Performance Evaluation and Quality Control in Clinical Molecular Genetics

Jarvis

Iyer

Williams

et al. 2005

The Journal of Molecular Diagnostics

Self Cite

View full text Add to dashboard Cite

The lack of readily available, patient-derived materials for molecular genetic testing of many heterozygous or rare disorders creates a major impediment for laboratory proficiency and quality control procedures. The paucity of clinically derived mutation-positive samples could be surmounted if it were possible to construct artificial samples containing mutations of interest that would sufficiently resemble natural human samples. Such samples could then function as acceptable and realistic performance evaluation challenges and quality control reagents for recipient laboratories. Using the cystic fibrosis gene (CFTR) as a prototype, we have devised and executed experiments designed to generate unique DNA samples that could be used for these purposes. We used site-directed mutagenesis to generate mutations of interest in plasmid DNA derived from common bacterial artificial chromosome sources containing the cystic fibrosis transmembrane conductance receptor gene. CFTR mutations G85E and 1078delT were chosen to represent mutations in the original American College of Medical Genetics-recommended populationscreening panel of 25 mutations. DNA samples containing predetermined concentrations and ratios of wild-type and mutated plasmids, bacterial artificial chromosomes of interest, and nonhuman genomic carrier DNA were characterized and tested in-house and in a group of nine pilot testing laboratories using a variety of technical platforms. The results indicate that these constructs, containing CFTR mutations in heterozygous and homozygous states, can serve as valid and accessible materials for quality assurance, including performance evaluation, proficiency test-

show abstract

Section: Sample Construction and Preparationmentioning

confidence: 99%

A Novel Method for Creating Artificial Mutant Samples for Performance Evaluation and Quality Control in Clinical Molecular Genetics

Jarvis

Iyer

Williams

et al. 2005

The Journal of Molecular Diagnostics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Carrier screening was performed with four targeted mutation panels: the ACMG-recommended core panel with 23 mutations, 7 the Integrated Genetics CFplus panel with 92 CFTR mutations, 9 the Counsyl Family Prep Screen 1.0 panel with 103 CFTR mutations, 8 and the Recombine CarrierMap panel with 108 CFTR mutations (http://www.recombine.com, accessed on 20 January 2015). In addition, mock screening was performed with the hypothetical targeted mutation panel representing the 159 variants characterized by Sosnay et al 11 in genomes from the CFTR2 patient cohort.…”

Section: Cystic Fibrosis Mutation Screening Panelsmentioning

confidence: 99%

“…For this purpose, a core panel of 23 variants has been assembled based on strict selection criteria of classic disease presentation and a CF patient chromosome frequency of more than 0.1. 6,7 The ACMG also recommends that mutations selected for inclusion on any DNA-based panel should be representative of the existing "pan-ethnic United States population. " 7 Since the establishment of the core ACMG panel, numerous commercial laboratories have produced expanded genetic panels of 90 or more CFTR variants, including those designed by the genetic testing companies Integrated Genetics, Counsyl, and Recombine.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 The ACMG also recommends that mutations selected for inclusion on any DNA-based panel should be representative of the existing "pan-ethnic United States population. " 7 Since the establishment of the core ACMG panel, numerous commercial laboratories have produced expanded genetic panels of 90 or more CFTR variants, including those designed by the genetic testing companies Integrated Genetics, Counsyl, and Recombine. 8,9 Original research article Although DNA genotyping can be extraordinarily accurate from an analytical perspective, it is not sufficient by itself for determination of downstream effects of gene function and prediction of phenotypes in hypothesized homozygous or compound heterozygous individuals (see Cooper et al for a review 10 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk

Lim¹,

Silver²,

Silver³

et al. 2016

Genetics in Medicine

View full text Add to dashboard Cite

“…This recommended panel was recently modified and currently includes 23 mutations. 2 The selected panel chiefly reflects the mutations prevalent in the high-risk populations of Northern European and Askenazi Jewish descent. Mutations that are prevalent in other races and ethnicities are mostly not included in the routine CF 25 mutation panel because they do not reach inclusion criteria for the general population threshold.…”

mentioning

confidence: 99%

Genotyping Microarray for the Detection of More Than 200 CFTR Mutations in Ethnically Diverse Populations

Schrijver

Oitmaa

Metspalu

et al. 2005

The Journal of Molecular Diagnostics

View full text Add to dashboard Cite

Cystic fibrosis (CF), which is due to mutations in the cystic fibrosis transmembrane conductance regulator gene, is a common life-shortening disease. Although CF occurs with the highest incidence in Caucasians, it also occurs in other ethnicities with variable frequency. Recent national guidelines suggest that all couples contemplating pregnancy should be informed of molecular screening for CF carrier status for purposes of genetic counseling. Commercially available CF carrier screening panels offer a limited panel of mutations, however, making them insufficiently sensitive for certain groups within an ethnically diverse population. This discrepancy is even more pronounced when such carrier screening panels are used for diagnostic purposes. By means of arrayed primer extension technology, we have designed a genotyping microarray with 204 probe sites for CF transmembrane conductance regulator gene mutation detection. The arrayed primer extension array, based on a platform technology for disease detection with multiple applications, is a robust, costeffective, and easily modifiable assay suitable for CF carrier screening and disease detection. (J Mol Diagn 2005, 7:375-387)

show abstract

Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel

Cited by 419 publications

References 8 publications

A Novel Method for Creating Artificial Mutant Samples for Performance Evaluation and Quality Control in Clinical Molecular Genetics

A Novel Method for Creating Artificial Mutant Samples for Performance Evaluation and Quality Control in Clinical Molecular Genetics

Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk

Genotyping Microarray for the Detection of More Than 200 CFTR Mutations in Ethnically Diverse Populations

Contact Info

Product

Resources

About