The inequity of targeted cystic fibrosis reproductive carrier screening tests in Australia

Bennett O.V. Shum; Letitia M. F. Sng; Rasa Ruseckaite; Ilya Henner; Natalie Twine; Denis C. Bauer; Urs Wilgen; Carel Pretorius; Paulette Barahona; Jacobus P. J. Ungerer; Glenn Bennett

doi:10.1002/pd.6285

The inequity of targeted cystic fibrosis reproductive carrier screening tests in Australia

Bennett O.V. Shum, Letitia M. F. Sng, Rasa Ruseckaite, Ilya Henner, Natalie Twine, Denis C. Bauer, Urs Wilgen, Carel Pretorius, Paulette Barahona, Jacobus P. J. Ungerer^*, Glenn Bennett^*

^*Corresponding author for this work

Applied BioSciences

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Objective: European and Australian guidelines for cystic fibrosis (CF) reproductive carrier screening recommend testing a small number of high frequency CF causing variants, rather than comprehensive CFTR sequencing. The study objective was to determine variant detection rates of commercially available targeted reproductive carrier screening tests in Australia.

Methods: Next-generation DNA sequencing of the CFTR gene was performed on 2552 individuals from a whole population sample to identify CF causing variants. The variant detection rates of two commercially available Australian reproductive carrier screening tests, which target 50 or 175 CF causing variants, in this population were calculated. The ethnicity of individuals was determined using principal component analysis.

Results: Variant detection rates of the tests for 50 and 175 CF causing variants were 88.2% and 90.8%, respectively. No CF causing variants in individuals of East Asian ethnicity (n = 3) were detected by either test, while >86.6% (n = 69) of CF causing variants in Europeans would be identified by either test.

Conclusions: Reproductive carrier screening tests for a targeted set of high frequency CF variants are unable to detect approximately 10% of CF variants in a multiethnic Australian population, and individuals of East Asian ethnicity are disproportionally affected by this test limitation.

Original language	English
Pages (from-to)	109-116
Number of pages	8
Journal	Prenatal Diagnosis
Volume	43
Issue number	1
Early online date	15 Dec 2022
DOIs	https://doi.org/10.1002/pd.6285
Publication status	Published - Jan 2023

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@article{01ffc28dc6a64eaab19297fc5e54d54b,

title = "The inequity of targeted cystic fibrosis reproductive carrier screening tests in Australia",

abstract = "Objective: European and Australian guidelines for cystic fibrosis (CF) reproductive carrier screening recommend testing a small number of high frequency CF causing variants, rather than comprehensive CFTR sequencing. The study objective was to determine variant detection rates of commercially available targeted reproductive carrier screening tests in Australia. Methods: Next-generation DNA sequencing of the CFTR gene was performed on 2552 individuals from a whole population sample to identify CF causing variants. The variant detection rates of two commercially available Australian reproductive carrier screening tests, which target 50 or 175 CF causing variants, in this population were calculated. The ethnicity of individuals was determined using principal component analysis. Results: Variant detection rates of the tests for 50 and 175 CF causing variants were 88.2% and 90.8%, respectively. No CF causing variants in individuals of East Asian ethnicity (n = 3) were detected by either test, while >86.6% (n = 69) of CF causing variants in Europeans would be identified by either test. Conclusions: Reproductive carrier screening tests for a targeted set of high frequency CF variants are unable to detect approximately 10% of CF variants in a multiethnic Australian population, and individuals of East Asian ethnicity are disproportionally affected by this test limitation.",

author = "Shum, {Bennett O.V.} and Sng, {Letitia M. F.} and Rasa Ruseckaite and Ilya Henner and Natalie Twine and Bauer, {Denis C.} and Urs Wilgen and Carel Pretorius and Paulette Barahona and Ungerer, {Jacobus P. J.} and Glenn Bennett",

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doi = "10.1002/pd.6285",

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AU - Shum, Bennett O.V.

AU - Sng, Letitia M. F.

AU - Ruseckaite, Rasa

AU - Henner, Ilya

AU - Twine, Natalie

AU - Bauer, Denis C.

AU - Wilgen, Urs

AU - Pretorius, Carel

AU - Barahona, Paulette

AU - Ungerer, Jacobus P. J.

AU - Bennett, Glenn

PY - 2023/1

Y1 - 2023/1

N2 - Objective: European and Australian guidelines for cystic fibrosis (CF) reproductive carrier screening recommend testing a small number of high frequency CF causing variants, rather than comprehensive CFTR sequencing. The study objective was to determine variant detection rates of commercially available targeted reproductive carrier screening tests in Australia. Methods: Next-generation DNA sequencing of the CFTR gene was performed on 2552 individuals from a whole population sample to identify CF causing variants. The variant detection rates of two commercially available Australian reproductive carrier screening tests, which target 50 or 175 CF causing variants, in this population were calculated. The ethnicity of individuals was determined using principal component analysis. Results: Variant detection rates of the tests for 50 and 175 CF causing variants were 88.2% and 90.8%, respectively. No CF causing variants in individuals of East Asian ethnicity (n = 3) were detected by either test, while >86.6% (n = 69) of CF causing variants in Europeans would be identified by either test. Conclusions: Reproductive carrier screening tests for a targeted set of high frequency CF variants are unable to detect approximately 10% of CF variants in a multiethnic Australian population, and individuals of East Asian ethnicity are disproportionally affected by this test limitation.

AB - Objective: European and Australian guidelines for cystic fibrosis (CF) reproductive carrier screening recommend testing a small number of high frequency CF causing variants, rather than comprehensive CFTR sequencing. The study objective was to determine variant detection rates of commercially available targeted reproductive carrier screening tests in Australia. Methods: Next-generation DNA sequencing of the CFTR gene was performed on 2552 individuals from a whole population sample to identify CF causing variants. The variant detection rates of two commercially available Australian reproductive carrier screening tests, which target 50 or 175 CF causing variants, in this population were calculated. The ethnicity of individuals was determined using principal component analysis. Results: Variant detection rates of the tests for 50 and 175 CF causing variants were 88.2% and 90.8%, respectively. No CF causing variants in individuals of East Asian ethnicity (n = 3) were detected by either test, while >86.6% (n = 69) of CF causing variants in Europeans would be identified by either test. Conclusions: Reproductive carrier screening tests for a targeted set of high frequency CF variants are unable to detect approximately 10% of CF variants in a multiethnic Australian population, and individuals of East Asian ethnicity are disproportionally affected by this test limitation.

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The inequity of targeted cystic fibrosis reproductive carrier screening tests in Australia

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