Negative Harmony NIPT - Sequenom Laboratories

• Prior negative Harmony NIPT test • Fetal anomalies identified via ultrasound • Positive CMA (NOS) (chromosomal microarray not otherwise specified)...

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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.

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18 19 20 2122

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50kb bins

SPCA 50kb profile, 1612700163−NIK−2−20, auto MAD: 0.0445, scaled GC bias: 61.2, BFF: 0.142

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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.

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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

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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

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Genomic Location (Mb)

Chromosome 4 – 73.45 Mb duplication 4p16.3q13.3

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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