Diagnostic accuracy of random massively parallel sequencing for non-invasive prenatal detection of common autosomal aneuploidies: a collaborative study in Europe.
OBJECTIVE
The objective of this study is to validate the diagnostic accuracy of a non-invasive prenatal test for detecting trisomies 13, 18, and 21 for a population in Germany and Switzerland.


METHODS
Random massively parallel sequencing was applied using Illumina sequencing platform HiSeq2000. Fetal aneuploidies were identified using a median absolute deviation based z-score equation. A bioinformatics algorithm based on guanine-cytosine normalization was applied after the data were unblinded. Results of massively parallel sequencing and invasive procedures were compared.


RESULTS
Overall, 40/42 samples were correctly classified as trisomy 21-positive, including a translocation trisomy 21 [46,XY,der(13;21),+21] and a structural aberration of chromosome 21 [46,XX,rec(21)dup(21q)inv(21)(p12q21.1)] but not including a low percentage mosaic trisomy 21 [47,XY,+21/46,XY], [sensitivity: 95.2%; one-sided lower confidence limit: 85.8%]; 430/430 samples were correctly classified as trisomy 21-negative (specificity: 100%; one-sided lower CL: 99.3%). Using a new bioinformatics algorithm with guanine-cytosine normalization, detection of trisomy 21 was facilitated, and five of five trisomy 13 cases and eight of eight trisomy 18 cases were correctly identified.


CONCLUSIONS
Our newly established non-invasive prenatal test allows detection of fetal trisomies 13, 18, and 21 with high accuracy in a population in Germany and Switzerland.
Zentrum für Pränataldiagnostik und Humangenetik, Berlin, Germany.
Markus
M
Stumm
Michael
M
Entezami
Karsten
K
Haug
Cornelia
C
Blank
Max
M
Wüstemann
Bernt
B
Schulze
Gisela
G
Raabe-Meyer
Maja
M
Hempel
Markus
M
Schelling
Eva
E
Ostermayer
Sabine
S
Langer-Freitag
Tilo
T
Burkhardt
Roland
R
Zimmermann
Tina
T
Schleicher
Bernd
B
Weil
Ulrike
U
Schöck
Patricia
P
Smerdka
Sebastian
S
Grömminger
Yadhu
Y
Kumar
Wera
W
Hofmann
D000328:Adult; D000465:Algorithms; D000649:Amniocentesis; D000782:Aneuploidy; D015193:Chorionic Villi Sampling; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005858:Germany; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D013557:Switzerland; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome; D055815:Young Adult