臨床婦人科産科73巻2号

2019年03月発行

今月の臨床 NIPT新時代の幕開け―検査の実際と将来展望 NIPTの将来展望

全ゲノムNIPTではどこまで胎児異常が検索できるか？

著者： 福島明宗¹ 小畑慶子¹ 山本佳世乃¹

所属機関： ¹岩手医科大学医学部臨床遺伝学科

ページ範囲：P.258 - P.261

●NIPTによる全ゲノム解析（genome-wide NIPT）が可能な時代になっている．

●本検査は7Mbレベルでの欠失/重複分析が可能である．

●非確定的遺伝学的検査であり，コピー数バリアント（CNV）の確定には染色体マイクロアレイを行う必要がある．

●幅広い臨床遺伝学領域を網羅するためには，エビデンスの集積が必要である．

参考文献

1）黒澤健司 : 総説 特集 : ICSIの可能性と問題点　出生児の染色体異常とその診断方法．J Mamm Ova Res 30 : 145-148, 2013

2）Shaffer LG, et al : Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound. Prenat Diagn 32 : 986-995, 2012

3）Wapner RL, et al : Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 367 : 2175-2184, 2012

4）Hayward J, et al : Beyond screening for chromosomal abnormalities : advances in non-invasive diagnosis of single gene disorders and fetal exsome sequencing. Semin Fetal Neonatal Med 23 : 94-101, 2018

5）Lefkowitz RB, et al : Clinical validation of a noninvasive prenatal testfor genome wide detection of fetal copy number variants. Am J Obstet Gynecol 215 : 227. e1-227.e16, 2016

6）Di Gregorio E, et al : Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH. Mol Cytogenet 7 : 82, 2014

7）Norton ME, et al : Cell-free DNA vs sequential screening for the detection of fetal chromosomal abnormalities. Am J Obstet. Gynecol 214 : 727, e1-6, 2016

8）Miller RG : Simultaneousstatistical inference. 2nd ed. New York : Springer-verlang, 1981

9）Wapner RJ, et al : Expanding the scope of noninvasive prenatal testing : detection of fetal microdeletion syndromes. Am J Obstet Gynecol 212 : 332, e1-9, 2015

10）Zhao C, et al : Detection of fetal subchromosomal abnormalities by sequencing circulating cell-free DNA from maternal plasma. Clin Chem 61 : 608-616, 2015

11）Mark D. Pertile, Noninvasive Prenatal Testing（NIPT） Chapter 7 Genome-wide cell-free DNA-Based prenatal testing for rare autosomal trisomies and subchromosomal Abnormalities. P110, ACADEMIC PRESS London 2018.

12）American College of Obstetricians and Gynecologists. Committee opinion no.640 : Cell-free DNA screening for fetal aneuploidy 18 : 1056-1065, 2016

13）Gregg AR, et al : Noninvasive prenatal screening for fetal aneuploidy 18 : 1056-1065, 2016

14）Salomon LJ, et al : ISUOG updated consensusstatement on the impact of cfDNA aneuploidy testing on screening policies and prenatal ultrasound practice. Ultrasound Obstet Gynecol 49 : 815-816, 2017

15）Pertiles MD, et al : Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggestincreased risk of feto-placental disease. Sci Transl Med 9（405）, 2017

16）Van Opstal D, et al : Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS : results of the TRIDENTstudy. Genet Med 20 : 480-485, 2018

17）Ehrich M, et al : Genome-wide cfDNA screening : clinical laboratory experience with thefirst10,000 cases. Genet Med 19 : 1332-1337, 2017

18）Chen S, et al : A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallels sequencing. Prenat Diagn 33 : 584-590, 2013

19）Brady P, et al : Clinical implementation of NIPT-technical and biological challenges. Clin Genet 89 : 523-530, 2016

20）Fiorentino F, et al : The clinical utility of genome-wide non-invasive prenatal screening. Prenat Diagn 37 : 593-601, 2017

21）Schwartz S, et al : Clinical experience of laboratory follow-up with noninvasive prenatal testing using cell-free DNA and positive microdeletion results in 349 cases. Prenat Diagn 38 : 210-300, 2018

22）Martin K, et al : Clnincal experience with a single nucleotide polymerism-based non-invasive prenatal testforfive clinically signify microdeletions. Clin Genet 93 : 293-300, 2018

23）Brison N, et al : Predicting fetoplacental chromosomal mosaicium during noon-invasive prenatal testing. Prenat Diagn 38 : 258-266, 2018

24）Wilkins-Haug L, et al : Biological explanations for discordant noninvasive prenatal testresults : prelim data and lessons learned. Prenat Diagn 38 : 445-448, 2018