Genomic Sequencing in Womens Health Mary E Norton, MD Department - - PDF document
12/6/19 Genomic Sequencing in Womens Health Mary E Norton, MD Department of Obstetrics, Gynecology, and Reproductive Sciences University of California, San Francisco 1 Disclosures Research funding from Natera Consultant to Invitae
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Mary E Norton, MD Department of Obstetrics, Gynecology, and Reproductive Sciences University of California, San Francisco 1
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Patient produces 23andMe document
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Detection
men only)
men only)
for men only)
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Uses/ Benefits
studies
Challenges/Risks
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healthcare professional for recommended screenings or appropriate follow-up. Results should be confirmed in a clinical setting before taking any medical action. “
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undergone a general quality review; however, only a subset
The data from 23andMe’s Browse Raw Data feature is suitable only for informational use and not for medical, diagnostic or other use. Consult with a healthcare professional before making any major lifestyle changes.”
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N=49 samples
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predetermined sites) vs. full-gene sequencing with del/dup analysis
data variant ØThis is not a substitute for clinical testing!
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Down syndrome No Yes Terminate pregnancy No Yes
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(Gil et al, Ultrasound Obstet Gynecol, 2015
(Gil et al, Ultrasound Obstet Gynecol, 2017)
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20 40 60 80 100 120 A g e > 3 5 T r i p l e s c r e e n Q u a d s c r e e n F i r s t t r i m e s t e r s c r e e n I n t e g r a t e d s c r e e n c f D N A
Detection Rate (%)
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Down syndrome 22q deletion syndrome Cystic fibrosis
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Most of these are for inherited disorders
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distinguished
is Rh positive
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achondroplasia
Chitty LS, et al. Prenat Diagn 35:656, 2015
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advanced paternal age
performance
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Structural Malformations
Autosomal recessive Autosomal dominant X-linked Chromosomal/ karyotype
Chromosomal microarray
sequencing
screening
Copy number variants
Ultrasound
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Unaffected carriers Affected
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Unaffected carriers Affected
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Screening for Affected
Screening for Carriers 2 w k s
Conception
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consent
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1. Hemoglobinopathies 1970’s 2. Tay Sachs disease 1971 3. Canavan disease 1998 4. Cystic fibrosis 2001 5. Familial dysautonomia 2004 6. Spinal muscular atrophy 2008 (ACMG) 7. Spinal muscular atrophy 2017 (ACOG) 8. Expanded Jewish panel 2008 (ACMG) 9. Expanded Jewish panel 2017 (ACOG) 10. Expanded carrier screening 2017 (ACOG) 57
Sickle cell disease Tay-Sachs disease 58
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Utilization of new technologies to identify carriers of hundreds of genetic conditions simultaneously
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Disorder is important à test is developed and introduced Technology is developed à test is introduced
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Disorders should be:
phenotype
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What criteria are required by laboratories before adding variants to panels? Test is available
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and ACOG
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24-45% will have something
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during first pregnancy (in NY)
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normal
reclassified as benign
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