Non-invasive prenatal diagnosis of achondroplasia and thanatophoric dysplasia: next-generation sequencing allows for a safer, more accurate, and comprehensive approach

Prenatal Diagnosis
Lyn S ChittyLucy Jenkins

Abstract

Accurate prenatal diagnosis of genetic conditions can be challenging and usually requires invasive testing. Here, we demonstrate the potential of next-generation sequencing (NGS) for the analysis of cell-free DNA in maternal blood to transform prenatal diagnosis of monogenic disorders. Analysis of cell-free DNA using a PCR and restriction enzyme digest (PCR-RED) was compared with a novel NGS assay in pregnancies at risk of achondroplasia and thanatophoric dysplasia. PCR-RED was performed in 72 cases and was correct in 88.6%, inconclusive in 7% with one false negative. NGS was performed in 47 cases and was accurate in 96.2% with no inconclusives. Both approaches were used in 27 cases, with NGS giving the correct result in the two cases inconclusive with PCR-RED. NGS provides an accurate, flexible approach to non-invasive prenatal diagnosis of de novo and paternally inherited mutations. It is more sensitive than PCR-RED and is ideal when screening a gene with multiple potential pathogenic mutations. These findings highlight the value of NGS in the development of non-invasive prenatal diagnosis for other monogenic disorders.

References

Aug 16, 1997·Lancet·Y M LoJ S Wainscoat
Jul 29, 1999·Human Mutation·M R Passos-BuenoH Kitoh
Dec 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Fiona M F LunY M Dennis Lo
Jan 7, 2010·Fetal Diagnosis and Therapy·Ann Tabor, Zarko Alfirevic
Nov 26, 2010·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·L S ChittyT J Cole
May 21, 2013·Prenatal Diagnosis·Lyn S Chitty, Diana W Bianchi
May 21, 2013·Prenatal Diagnosis·Ashwin AgarwalSubhashini Chandrasekharan
Mar 13, 2014·The Journal of Clinical Endocrinology and Metabolism·Maria I NewY M Dennis Lo

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Citations

Oct 17, 2015·Annual Review of Medicine·Felix C K Wong, Y M Dennis Lo
Aug 16, 2015·Prenatal Diagnosis·Suzanne DruryLyn S Chitty
Sep 13, 2016·Prenatal Diagnosis·Amy M BremanArthur L Beaudet
Nov 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·K C Allen ChanYuk Ming Dennis Lo
Jan 26, 2017·European Journal of Human Genetics : EJHG·Michael ParksStephanie Allen
Jan 31, 2017·Current Opinion in Obstetrics & Gynecology·Stephanie AllenBenjamin Bowns
Jun 28, 2017·Prenatal Diagnosis·Sunayna BestLyn S Chitty
Mar 30, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Natalie ChandlerLyn S Chitty
Mar 16, 2018·Congenital Anomalies·Sumire TerasawaHiroki Kurahashi
Jun 17, 2018·Prenatal Diagnosis·Xinyao ZhouLuming Sun
Jul 3, 2018·Expert Review of Molecular Diagnostics·Rhiannon MellisLyn S Chitty
Jul 26, 2018·Genetics and Molecular Biology·Carolina MalcherMaria Rita Passos-Bueno
Aug 2, 2018·The New England Journal of Medicine·Diana W Bianchi, Rossa W K Chiu
Jan 10, 2018·Prenatal Diagnosis·Eunice Ka Long ChiuRossa Wai Kwun Chiu
Jan 31, 2018·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·A J VivantiA Benachi
Nov 18, 2016·F1000Research·Ignatia B Van den Veyver
Jun 30, 2018·Archives of Disease in Childhood. Fetal and Neonatal Edition·Rachel Helen Horton, Diana Gay Wellesley
Jun 8, 2019·Prenatal Diagnosis·Eva Pajkrt, Lyn S Chitty
Nov 23, 2019·Cells·Valentina Karin-KujundzicLjiljana Serman
Nov 4, 2017·Clinical Chemistry·Joan Camunas-SolerStephen R Quake
Dec 18, 2019·Clinical Chemistry·Elizabeth ScotchmanLyn S Chitty
Feb 26, 2020·Journal of Perinatology : Official Journal of the California Perinatal Association·Monica H WojcikPankaj B Agrawal
Jan 1, 2020·Prenatal Diagnosis·Eva MelerAntoni Borrell
Apr 12, 2020·Prenatal Diagnosis·Aldesia ProvenzanoSabrina Giglio
Oct 11, 2017·Clinical Obstetrics and Gynecology·Anthony R Gregg
Nov 9, 2019·Human Genetics·Ahmad Abou Tayoun, Heather Mason-Suares
Dec 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Mary E Norton
Jun 22, 2017·Journal of Psychosomatic Obstetrics and Gynaecology·Blanche GriffinCeline Lewis
Oct 5, 2017·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·F FuC Liao

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Methods Mentioned

BETA
blood draw
PCR
Assay
electrophoresis

Software Mentioned

PCR
Primer
RED

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