CLINICAL UPDATE
MaterniT® GENOME case study 3 Bulletin 4 | August 2016
1 4
Hx 31 YEAR OLD FEMALE
Finding
24 WEEKS GA • •
MATERNIT GENOME ORDERED AT 24 WEEKS* Positive: 14.6 Mb duplication 1q42.2q44 73.45 Mb duplication 4p16.3q13.3
Prior negative Harmony NIPT test Fetal anomalies identified via ultrasound Positive CMA (NOS)
•
(chromosomal microarray not otherwise specified)
BASELINE TRACE
(Lab Director comment: “These results raise the possibility of a supernumerary der(4)(1q;4p).”)
1.4
Normal 50 Kb trace (for comparison)
0.8
1.0
1.2
Each number represents a chromosome, from 1 to 22, X/Y. Note that the orange line stays relatively flat in a normal trace.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16 17
18 19 20 2122
X
Y
0.6
1
0
10000
20000
30000
40000
50000
50kb bins
SPCA 50kb profile, 1612700163−NIK−2−20, auto MAD: 0.0445, scaled GC bias: 61.2, BFF: 0.142
1.4
Positive MaterniT GENOME trace
CASE STUDY TRACE 18 19 20 2122
X
Y
q23.1
q21.3
q21.1
q14.3
q14.1
q13.2
q12.3
q12.1
p12
q11.1
p13.2
p14.1
p14.3
p15.2
q22.2 q22.3
16 17
q22.1
15
q21.2
14
q15
13
q14.2
12
q13.3
11
q13.1
10
q12.2
9
q11.2
8
p11
7
p13.1
6
p13.3
5
p14.2
4
p15.1
3
p15.31
2
0.0
1.2
0.5
0.6
1.0
1
p15.33
1.4
1.5
p15.32
2.0
0.8
1.0
1.2
Note the significant upward deviation on the orange line for chromosome 1q and for chromosome 4p signifying a gain of material on both chromosomes.
0
0
10000
20000
30000
40000
10
20
30
40
50
60
70
80
90
100
110
12
Genomic Location (Mb)
50000
1.0
50kb bins
18 19 20 2122
X
Y
q13
16 17
q12.2
15
q12.1
14
q11.2
13
q11.1
12
p11.1
11
p11.2
10
p12.1
9
p12.2
8
p12.3
7
p13.11
6
p13.13
5
p13.2
4
p13.3
3
1.5
2
1.0
.6
1
p13.12
2.0
0.8
*Post CMA at the request of the clinician for research purposes.
CLINICAL UPDATE
MaterniT® GENOME case study 3 Bulletin 4 | August 2016
Key points •
MaterniT GENOME correctly identified complex chromosomal abnormalities following an ultrasound finding suggestive of different chromosomal and genetic conditions, confirmed by diagnostic testing MaterniT GENOME detects chromosomal abnormalities not detected by Harmony As illustrated by this case study, using traditional NIPT and screening for only common aneuploidies (T13/18/21) may miss clinically relevant abnormalities on other chromosomes, potentially delivering false reassurance
• •
Summary: MaterniT GENOME is the only genome-wide NIPT to date; it detects up to 30% more chromosomal information than other NIPTs1; detects chromosomal aneuploidies missed by traditional NIPT; and thereby providing earlier awareness and more proactive pregnancy management options
q43
q42.2
q44
q42.3
q42.13
q41
q42.11
q42.12
q32.2 q32.3
q32.1
q31.3
q31.1 q31.2
q25.2 q25.3
q24.3 q25.1
q24.1 q24.2
q22
q23.2
q23.1
q23.3
q21.2 q21.3
q21.1
q12 q11
p11.2
p12
p11.1
p13.2
p13.1
p21.1 p13.3
p21.3 p21.2
p22.2 p22.1
p22.3
p31.1
p31.3 p31.2
p32.2 p32.1
p32.3
p33
p34.2 p34.1
p35.1
p35.2
p34.3
p35.3
p36.12 p36.11
p36.21 p36.13
p36.23 p36.22
p36.31
1.0 0.5 0.0
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
210
220
230
240
250
Genomic Location (Mb)
Chromosome 1 – 14.6 Mb duplication 1q42.2q44
q35.1 q35.2
q34.3
q34.2 q34.1
q33
q32.2 q32.3
q31.3 q32.1
q31.1
q31.22 q31.23
q31.21
q28.3
q27
q28.2 q28.1
q25
q26
q24
q22.3
q23
q22.2
q21.22
q21.3 q22.1
q21.23
q21.1 q13.3
q21.21
q13.2 q13.1
q12
p11 q11
p12
p13 p14
p15.2
p15.1
p15.31 p15.32
p16.1
0.0
0.5
1.0
1.5
p16.3
p16.2
p15.33
2.0
1612700163−NIK−2−20, chr4p16.3q13.3, base: 100001:73550000, size(Mb): 66.45 [73.45], CBS z−score: 41.24, CBS LOR: 1000, chr z−score: 17.75, chr LOR: 128, CBS est FF: 0.13, chrXFF: 0.12, bff: 0.142, profile SD: 0.0455, bst_subchr: 1, maternal: FALSE
SPCA Profile
SPCA Profile
1.5
p36.33
p36.32
2.0
1612700163−NIK−2−20, chr1q42.2q44, base: 234600001:249200000, size(Mb): 13.35 [14.6], CBS z−score: 19.66, CBS LOR: 190.53, chr z−score: 3.12, chr LOR: −45.8, CBS est FF: 0.12, chrXFF: 0.12, bff: 0.142, profile SD: 0.0455, bst_subchr: 1, maternal: FALSE
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
Genomic Location (Mb)
Chromosome 4 – 73.45 Mb duplication 4p16.3q13.3
180
190
200
Ideograms from the MaterniT GENOME lab report with close up views of each impacted chromosomal trace provide a detailed view of the regions of interest. The purple shows the deviations: a gain on chromosome 1q and gain on chromosome 4p (Note the purple trace in relation to the blue trace).
Case study 3 summary • • • • •
Initial ultrasound suggested fetal anomalies MaterniT GENOME ordered (24 weeks, ultrasound only) – positive for gain on chromosomes 1 and 4 Maternal balanced translocation (1;4) subsequently detected by karyotype MaterniT GENOME test results confirmed by diagnostic testing MaterniT GENOME test results identified chromosomal abnormalities not detected by the Harmony test
1. Incidence of fetal chromosomal and subchromosomal abnormalities based on Wellseley et al. Eur J Hum Genet. 2012 May; 20(5):521-6. Results from case studies are not predictive of results in other cases. Results in other cases may vary. © 2016 Sequenom, Inc. All rights reserved. SEQUENOM®, MaterniT® and Sequenom Laboratories™ are trademarks of Sequenom, Inc. MaterniT® GENOME is a laboratory-developed test that was developed and is performed exclusively by Sequenom Laboratories. 31-20575R1.3 0816
