Exome‐based preconception carrier testing for consanguineous couples in China

Abstract Purpose Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% risk of affected offspring as a consequence. Until recently, comprehensive preconception carrier testing (PCT) for AR disorders was unavailable in routine diagnostics. Here we developed and implemented such a test in routine clinical care. Methods We performed exome sequencing (ES) for 100 consanguineous couples. For each couple, rare variants that could give rise to biallelic variants in offspring were selected. These variants were subsequently filtered against a gene panel consisting of ~2,000 genes associated with known AR disorders (OMIM-based). Remaining variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, after which only likely pathogenic and pathogenic (class IV/V) variants, present in both partners, were reported. Results In 28 of 100 tested consanguineous couples (28%), likely pathogenic and pathogenic variants not previously known in the couple or their family were reported conferring 25% risk of affected offspring. Conclusion ES-based PCT provides a powerful diagnostic tool to identify AR disease carrier status in consanguineous couples. Outcomes provided significant reproductive choices for a higher proportion of these couples than previous tests.

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Challenges in Providing Residual Risks in Carrier Testing

Prenatal Diagnosis ◽

10.1002/pd.5975 ◽

2021 ◽

Author(s):

Robert Luke Nussbaum ◽

Robert Nathan Slotnick ◽

Neil J. Risch

Keyword(s):

Carrier Testing

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Carrier testing in the fragile X syndrome: Attitudes and opinions of obligate carriers

American Journal of Medical Genetics ◽

10.1002/(sici)1096-8628(19970110)68:1<62::aid-ajmg12>3.0.co;2-m ◽

1997 ◽

Vol 68 (1) ◽

pp. 62-69 ◽

Cited By ~ 39

Author(s):

Allyn McConkie-Rosell ◽

Gail A. Spiridigliozzi ◽

Timothy Iafolla ◽

Jack Tarleton ◽

Ave M. Lachiewicz

Keyword(s):

Fragile X Syndrome ◽

Fragile X ◽

Carrier Testing

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0216 The benefit of carrier testing in Duchenne and Becker muscular dystrophy families with known deletions

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(05)80588-x ◽

2005 ◽

Vol 238 ◽

pp. S155

Keyword(s):

Muscular Dystrophy ◽

Becker Muscular Dystrophy ◽

Carrier Testing

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Genetic Testing for Minors: Comparison between Italian and British Guidelines

Genetics Research International ◽

10.1155/2012/786930 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 4

Author(s):

Pamela Tozzo ◽

Luciana Caenazzo ◽

Daniele Rodriguez

Keyword(s):

Clinical Practice ◽

Genetic Testing ◽

Ethical Issues ◽

Social Issues ◽

Carrier Testing ◽

European Countries ◽

National Guidelines ◽

Common Framework ◽

Professional Guidelines

Genetic testing in children raises many important ethical, legal, and social issues. One of the main concerns is the ethically inappropriate genetic testing of minors. Various European countries established professional guidelines which reflect the different countries perspectives regarding the main ethical issues involved. In this paper, we analyze the Italian and the British guidelines by highlighting differences and similarities. We discuss presymptomatic, predictive, and carrier testing because we consider them to be the more ethically problematic types of genetic testing in minors. In our opinion, national guidelines should take into account the different needs in clinical practice. At the same time, in the case of genetic testing the national and supranational protection of minors could be strengthened by approving guidelines based on a common framework of principles and values. We suggest that the Oviedo Convention could represent an example of such a common framework or, at least, it could lead to articulate it.

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