The Cystic Fibrosis mutation “arms race”: when less is more

Grody, Wayne W.; Cutting, Garry R.; Watson, Michael S.

doi:10.1097/gim.0b013e318159a331

Cited by 57 publications

(44 citation statements)

References 31 publications

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“…The 23-mutation panel has performed well over the years and has met the expectations of a minimum CF carrier screening panel. 5,15 However, the panel does not perform as well in regions with a higher percentage of African Americans, Hispanic Americans, or members of other ethnic groups. 9,13,14,16 The ACMG/ACOG panel was originally designed for the Caucasian and Ashkenazi Jewish population and excludes mutations that are important in other ethnic groups "that are significant components of the American mosaic. "…”

Section: Discussionmentioning

confidence: 95%

“…1 Although CF is most prevalent in Caucasians (1 in 2,500), it is a panethnic disease in North America, found in all races, including African-American (1 in 15,000), Hispanic-American (1 in 13,500), and Asian-American (1 in 35,000) individuals. 5,6 This reflects the heterogeneity of the North American population. The incidence of CF in the North American population is primarily due to the higher-frequency alleles present mainly in the Caucasian population.…”

Section: Original Research Articlementioning

confidence: 95%

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Cystic fibrosis carrier screening in a North American population

Zvereff¹,

Faruki²,

Edwards³

et al. 2014

Genetics in Medicine

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Methods:Patients referred for cystic fibrosis screening from January 2005 through December 2010 were tested using either a 32-mutation panel (n = 1,601,308 individuals) or a 69-mutation panel (n = 109,830). Results:The carrier frequencies observed for the 69-mutation panel study population (1/36) and Caucasian (1/27) and African-American individuals (1/79) agree well with published cystic fibrosis carrier frequencies; however, a higher carrier frequency was observed for Hispanic-American individuals (1/48) using the 69-mutation panel as compared with the 32-mutation panel (1/69). The 69-mutation panel detected ~20% more mutations than the 32-mutation panel for both African-American and Hispanic-American individuals. Conclusion:Expanded panels using race-specific variants can improve cystic fibrosis carrier detection rates within specific populations. However, it is important that the pathogenicity and the relative frequency of these variants are confirmed. Genet Med advance online publication 19 December 2013

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Section: Discussionmentioning

confidence: 95%

Section: Original Research Articlementioning

confidence: 95%

Cystic fibrosis carrier screening in a North American population

Zvereff¹,

Faruki²,

Edwards³

et al. 2014

Genetics in Medicine

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“…With the implemented panel, however, differences between individual ethnic groups in detection rates do exist. For example, the detection rate among Hispanic CFTR mutation carriers is approximately 57%, compared with approximately 80%-97% in other whites (4 ), whereas the Hispanic carrier frequency of 1 in 46 is only modestly lower than that in Caucasians (1 in 29) (4 ) 14 ). Since the original implementation of CF carrier screening, the test has been widely implemented across the US, and a plethora of laboratory-developed and commercial assays that contain a minimum of the 23 recommended mutations have been adopted for clinical diagnostic use.…”

mentioning

confidence: 99%

Mutation Distribution in Expanded Screening for Cystic Fibrosis: Making Up the Balance in a Context of Ethnic Diversity

Schrijver

2011

Clinical Chemistry

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“…There is controversy over the appropriateness of CFTR mutation panels with more than the standard 23 mutations recommended by the American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists. 12 At the same time, not only are there Food and Drug Administration-cleared "kits" on the market that may be used to detect Ͼ23 mutations, but also, there are plausible reasons for enhanced numbers beyond the standard 23.…”

mentioning

confidence: 99%

The Suitability of Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry in a Laboratory Developed Test Using Cystic Fibrosis Carrier Screening as a Model

Farkas

Miltgen

Stoerker

et al. 2010

The Journal of Molecular Diagnostics

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We designed a laboratory developed test (LDT) by using an open platform for mutation/polymorphism detection. Using a 108-member (mutation plus variant) cystic fibrosis carrier screening panel as a model, we completed the last phase of LDT validation by using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Panel customization was accomplished via specific amplification primer and extension probe design. Amplified genomic DNA was subjected to allele specific , single base extension endpoint analysis by mass spectrometry for inspection of the cystic fibrosis transmembrane regulator gene (NM_000492.3). The panel of mutations and variants was tested against 386 blinded samples supplied by "authority" laboratories highly experienced in cystic fibrosis transmembrane regulator genotyping; >98% concordance was observed. All discrepant and discordant results were resolved satisfactorily. Taken together , these results describe the concluding portion of the LDT validation process and the use of mass spectrometry to detect a large number of complex reactions within a single run as well as its suitability as a platform appropriate for interrogation of scores to hundreds of

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The Cystic Fibrosis mutation “arms race”: when less is more

Cited by 57 publications

References 31 publications

Cystic fibrosis carrier screening in a North American population

Cystic fibrosis carrier screening in a North American population

Mutation Distribution in Expanded Screening for Cystic Fibrosis: Making Up the Balance in a Context of Ethnic Diversity

The Suitability of Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry in a Laboratory Developed Test Using Cystic Fibrosis Carrier Screening as a Model

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