TABLE OF CONTENTS (Not Final)
1.0
1.1
1.2
1.3
2.0
2.1
2.1.1
2.1.2
2.1.3
2.1.4
2.1.5
2.1.6
2.1.7.1
2.2
2.2.1
2.2.2
2.2.2.1
2.2.3
2.2.4
2.2.5
2.2.6
2.2.7
2.2.8
2.2.8.1
2.3
2.3.1
2.3.1.1
2.3.2
2.3.2.1
2.4
2.4.1
2.4.1.1
2.4.1.2
2.4.1.3
2.4.1.4
2.4.1.5
2.4.1.6
2.4.1.7
2.4.2
2.4.3
2.4.4
2.4.5
2.5
2.5.1
2.5.2
2.5.3
3.0
3.1
3.1.1
3.1.1.1
3.1.1.2
3.1.1.3
3.1.1.4
3.1.2
3.1.2.1
3.1.2.2
3.1.2.3
3.1.2.4
Introduction
20
Executive Summary
21
Objectives of This Report 23
Key Questions Answered in This Report
23
Prenatal Pregnancy Complications: An Overview
25
Advanced Maternal Age (AMA) 25
Risk for Down syndrome with Increased AMA
25
Risk of Miscarriage with Increased AMA 26
Risk of Cesarean Section with Increasing Maternal Age
27
Risk of Gestational Diabetes with Advanced Maternal Age
28
Risk for Pregnancy-Induced Hypertension with Advanced Maternal Age
29
Risk of Placenta Previa with Advanced Maternal Age 29
First Birth Rates for 35-39 Aged Women by Race in the U.S. 31
Pre-Existing Maternal Medical Conditions 32
Pregnancy Outcome in Women with Renal Disease 33
Pregnancy Outcome in Diabetic Women
34
Pregnancy Outcome in Women with Pre-Existing Thyroid Disease
34
Pregnancy Outcome in Obese Women
34
Pregnancy Outcome in Asthmatic Women 35
Pregnancy Outcome in Women with Epilepsy
36
Pregnancy Outcome in Women with Autoimmune Disease
36
Pregnancy Outcome in Women with Hemoglobinopathies
37
Pre-Existing Chronic Diseases among Women of Reproductive Ages in the U.S. 38
Chronic Disease Risk Behaviors and Risk Factors among Women of Reproductive Agein the U.S.
Medical Conditions Occurring during Pregnancy
40
Preeclampsia (Toxemia) 40
Prevalence of Preeclampsia in the U.S.
40
Gestational Diabetes
42
Prevalence of Gestational Diabetes (GDM) in the U.S.
42
Pregnancy-Related Issues 44
Premature labor 44
Common Medical Complications in Pre-Mature Babies
45
Global Prevalence of Preterm Births
45
Prevalence of Preterm Births in the U.S. by Stage
46
Prevalence of Preterm Births in the U.S. by Race/Ethnicity 46
Prevalence of Preterm Births in the U.S. by Plurality of Birth 47
Prevalence of Preterm Births in the U.S. by Maternal Age
48
Multiple Births in the U.S.
49
Placenta Previa 50
Breech Presentation
50
Meconium Stained Liquor 50
Oligohydramnios and Polyhydramnios
51
Fetal Problems 52
Fetal Growth Restriction 52
Imperforate Anus 52
Congenital Heart Disease 53
Types of Genetic Diseases in Fetuses: An overview 54
Single Gene Disorders
54
Autosomal Dominant Genetic Disorders
54
Huntington Disease (HD) 55
Familial hypercholesterolaemia (FH)
56
Marfan syndrome
56
Myotonic dystrophy
57
Autosomal Recessive Genetic Disorders
58
Cystic Fibrosis (CF)
59
Canavan Disease 62
Neutropenia
63
Ellis-van Creveld Syndrome (EVC)
63
3.1.2.5
3.1.2.6
3.1.2.7
3.1.2.8
3.1.2.9
3.1.2.10
3.1.2.11
3.1.2.12
3.1.2.13
3.1.2.14
3.1.2.15
3.1.3
3.1.3.1
3.1.3.2
3.1.3.3
3.1.3.4
3.1.3.5
3.1.4
3.1.4.1
3.1.4.2
3.1.4.3
3.1.4.4
3.1.4.5
3.1.4.6
3.1.4.7
3.1.4.8
3.1.4.9
3.2
3.2.1
3.2.1.1
3.2.2
3.2.2.1
3.2.3
3.2.3.1
3.2.4
3.2.4.1
3.2.5
3.2.5.1
3.2.5.2
3.2.5.3
3.2.6
3.2.6.1
3.2.6.2
3.2.7
3.2.7.1
3.2.8
3.2.8.1
3.2.8.2
3.2.9
3.2.9.1
3.2.10
3.2.11
3.2.12
3.2.13
3.3
3.3.1
3.3.1.1
3.3.1.2
3.3.1.3
3.3.2
Familial Mediterranean fever (FMF)
64
Fanconi Anemia (FA)
64
Gaucher Disease 64
Mucopolysaccharidosis (MPSs) 65
Phenylketonuria (PKU) 66
Sickle Cell Disease
66
Beta Thalassaemia
67
Inheritance Pattern of Autosomal Recessive Genetic Disorders
68
Chances of Inheriting a Single Gene Disorder
70
Common Recessive Disease Traits in Selected Ethnic Groups 71
Comprehensive List of Common Single Gene Disorders
71
X-Linked Dominant Genetic Disorders
73
Hypophosphotemic Rickets
73
Incontinentia Pigmenti 74
Focal Dermal Hypoplasia 74
Orofaciodigital Syndrome 74
Inheritance of Sex-Linked Dominant Disorders
75
X-Linked Recessive Disorders
76
Lesch-Nyhan Syndrome 76
Menkes Disease (Kinky hair syndrome)
77
Hemophilia A and B
77
Fabry’s Disease 78
Wiskott-Aldrich Syndrome (WAS) 79
Bruton’s Aggamaglobulinemia
79
Color Blindness 80
Complete Androgen Insensitivity Syndrome 80
Inheritance of X-Linked Recessive Traits 80
Chromosomal Disorders 82
47, XXY (Klinefelter Syndrome) 83
Prenatal Diagnosis of Klinefelter Syndrome 83
47, XYY Syndrome
84
Diagnosis of 47, XYY Syndrome 84
45, X Syndrome (Turner Syndrome)
84
Prenatal Diagnosis of Turner Syndrome
85
47, XXX (Triple X Syndrome)
85
Tests and Diagnosis for Triple X Syndrome 86
Trisomy 21
86
Tests and Diagnosis of Trisomy 21 86
Incidence of Down Syndrome by Maternal Age
87
Developmental Delay in Down syndrome Children 88
Trisomy 18 (Edward’s Syndrome) 89
Prenatal Diagnosis of Trisomy 18 89
Clinical Manifestations of Edward’s Syndrome
89
Trisomy 13 (Patau Syndrome)
90
Prenatal Diagnosis of Trisomy 13 91
Triploid Syndrome
91
Congenital Anomalies Associated with Triploidy
92
Prenatal Diagnosis of Triploidy
93
Prevalence of Trisomies in the U.S. 93
Trisomies and Abortions 93
Maternal Age-Related Frequencies of Aneuploid Fetuses
94
Clinical Features of Common Autosomal or Sex Chromosome Aneuploidy
95
Maternal Age and Aneuploidy
95
Sensitivity and Specificity of Maternal Serum and Ultrasound Tests for Aneuploids
Structural Chromosomal Abnormalities
97
Autosomal Deletions
97
Wolf-Hirschhorn Syndrome (WHS)
97
Cri du chat Syndrome
98
Langer-Giedion Syndrome
98
Common Autosomal Microdeletion Syndromes
99
96
3.3.2.1 Williams syndrome
100
3.3.2.2 WAGR Syndrome
101
3.3.2.3 Prader-Willi Syndrome (PWS)
101
3.3.2.4 Angelman Syndrome
103
3.3.2.5 Miller-Dicker Syndrome 103
3.3.2.6 Smith-Magenis Syndrome (SMS) 104
3.3.2.7 Alagille Syndrome (ALGS)
105
3.3.2.8 CATCH 22 Syndrome
105
3.3.2.9 DiGeorge Syndrome
106
3.3.3
Autosomal Duplication Syndromes 107
3.3.3.1 Beckwith-Wiedemann Syndrome (BWS) 107
3.3.3.2 Charcot-Marie-Tooth Disease Type 1A (CMTI)
109
3.3.3.3 Cat-Eye Syndrome
109
3.3.3.4 Appropriate Technologies for the Detection of Microdeletions, Duplication, Copy Number Variation
and Translocation110
4.0
Reproductive Genetic Counseling: An Overview
111
4.1
Impact of Recent Advances in Clinical Genomics on Genetic Counseling
112
5.0
Prenatal Screening for Genetic Diseases: An Overview
113
5.1
Routine Prenatal Screening Tests 113
5.2
Less-Routine Prenatal Screening Tests
113
5.3
Beta Human Chorionic Gonadotropin (β-hCG) Screening Test 114
5.3.1
hCG Kits and Manufacturers
115
5.4
First Trimester Pregnancy-Associated Plasma Protein-A (PAPP-A) Screening Test
115
5.5
Maternal Serum Alpha-Fetoprotein (MSAFP) Screening Test 116
5.6
Second Trimester Serum β-hCG Screening Test
116
5.7
Second Trimester Unconjugated Estriol (uE3) Screening Test 116
5.8
Second Trimester Inhibin-A Screening Test 117
5.9
Second Trimester Maternal Hexosaminidase Screening Test 117
5.10
Second Trimester Triple-Screen and Quad Screen Tests
117
5.11
Second Trimester Screening of Cell-Free Fetal DNA (cffDNA)
118
5.11.1 Sensitivity and Specificity of NIPT 118
5.11.2 Diagnostic Applications of cffDNA
119
5.11.3 Time of Availability of cffDNA in Maternal Blood 119
5.11.4 The Cost of NIPT Testing 120
5.11.5 Cost of NIPTs by Product 120
5.11.6 History of Aneuploidy Testing from 1970s to 2011 Culminating in NIPTs
121
5.11.7 NIPT Methods of Detecting Aneuploidy
121
5.11.7.1 Shotgun Method 121
5.11.7.2 Targeted Massively Parallel Sequencing (t-MPS)
121
5.11.7.3 Single-Nucleotide Polymorphisms (SNPs) 121
5.11.8 Comparison of Amniocentesis and NIPTs 122
5.11.9 Advantages of NIPTs
122
5.11.10 Disadvantages of NIPTs 123
5.11.11 Comparison of Some Performance Criteria for the commonly used Prenatal Tests
123
5.11.12 Comparison of NIPT Detection Rate with Traditional Screening Tests 124
5.11.13 False Positive Rates of NIPTs Compared with those of Conventional Screening Tests
124
5.11.14 Fetal Genetic Disorders Detectable by NIPTs and Other Screening Tests
124
5.12
First Trimester Ultrasound Screening Test 125
5.12.1 Nuchal Translucency (NT) Screening Test 125
5.12.2 Reliability of NT Test
126
5.13
Magnetic Resonance Imaging (MRI) in Prenatal Screening
127
5.14
Prenatal Diagnosis of Genetic Disorders
127
5.14.1 Amniocentesis (AC)
128
5.14.1.1 Reliability of Amniocentesis
128
5.14.2 Chorionic Villus Sampling (CVS) Diagnostic Test 128
5.14.2.1 Reliability of CVS Test 129
5.14.3 Cordocentesis or Percutaneous Umbilical Blood Sampling (PUBS)
130
5.15
Advantages and Disadvantages of Prenatal Diagnostic Tests 130
5.16
Future of Invasive Prenatal Tests 131
5.16.1 Indispensability of Invasive Tests 132
5.17
5.17.1
5.18
6.0
6.1
6.2
6.3
6.4
6.4.1
6.4.1.1
6.4.2
6.4.2.1
6.4.2.2
6.4.2.3
6.4.3
6.4.3.1
6.4.3.2
6.4.3.3
6.4.4
6.4.4.1
6.4.4.2
6.4.5
6.4.5.1
6.4.5.2
6.4.6
6.4.6.1
6.4.6.2
6.4.6.3
6.4.7
6.4.7.1
6.4.7.2
6.4.7.3
6.4.8
6.4.8.1
6.4.8.2
7.0
7.1
7.1.1
7.1.2
7.1.3
7.1.4
7.1.5
7.1.6
7.2
7.3
7.4
7.5
8.0
8.1
8.1.1
8.1.2
8.1.3
8.2
8.2.1
8.3
8.3.1
8.4
8.4.1
8.5
8.5.1
Intact Circulating Fetal Cells for Noninvasive Prenatal Tests 132
Scheme for Isolating Intact Fetal Cells for Prenatal Diagnosis 133
Trophoblast Retrieval and Isolation from Cervix (TRIC)
134
Newborn Genetic Screening
135
Status of Newborn Screening in Developed and Developing Countries 136
Status in Middle East and North Africa (MENA)
136
Screening Tests Recommended for All Newborns in the U.S. 137
The Most Common Newborn Genetic Disorders
139
Phenylketonuria (PKU) 139
Screening Techniques used for Diagnosis of PKU 140
Congenital Hypothyroidism (CHT) 140
Inheritance of CHT
140
Signs and Symptoms of CHT
140
Diagnosis of CHT
140
Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) 141
Inheritance of 21-OHD CAH
141
Symptoms of 21-OHD CAH
141
Diagnosis of 21-OHD CAH
141
Galactosemia
141
Signs and Symptoms of Galactosemia
142
Diagnosis of Galactosemia
142
Sickle Cell Anemia (SCD)
142
Symptoms of SCD
142
Tests and Diagnosis of SCD
142
Biotidinase Deficiency 143
Inheritance of Biotidinase Deficiency
143
Signs and Symptoms of Biotidinase Deficiency
143
Diagnosis of Biotidinase Deficiency
143
Hypocystinuria 144
Inheritance of Hypocystinuria
144
Signs and Symptoms of Hypocystinuria
144
Diagnosis of Hypocystinuria
144
Maple Syrup Urine Disease (MSUD)
144
Inheritance of MSUD
145
Diagnosis of MSUD
145
Preimplantation Genetic Screening and Preimplantsion Genetic Diagnosis (PGS/PGD)
PGS/PGD Technologies 146
Fluorescent in situ Hybridization (FISH)
146
Array Comparative Genome Hybridization (aCGH) 147
Single Nucleotide Polymorphism (SNP) Microarray 147
Oligonucleotide Genome Sequencing (OGS) 147
Express Genome Screening (EGS) 147
Next-Generation Sequencing (NGS)
147
Strengths and Weaknesses of Currently Available PGS/PGD Technologies
147
Genetic Diseases Detected during PGD
148
PGS/PDD Testing Products in the Market 153
Cost of PGD
154
Pregnancy, Prenatal, Newborn and PGD-Related Testing Technologies: An overview
Beta human chorionic gonadotropin (β-hCG) Test
156
Set-Up of the Test Strip (hCG)
156
Test Procedure (hCG)
157
Interpretation of the Result (hCG) 157
Pregnancy Associated Plasma Protein-A (PAPP-A) Test
158
Principle of PAPP-A Test 158
Maternal Serum Alpha Fetoprotein (MSAFP) Test 158
Principle of the Test (MSAFP)
158
Unconjugated Estriol (uE3) Test 159
Principle of the Assay (uE3)
159
Inhibin A Test 159
Principle of the Test (Inhibin A)
159
146
156
8.6
8.7
8.8
8.8.1
8.8.2
8.8.2.1
8.8.3
8.8.3.1
8.8.3.2
8.8.3.3
8.8.3.4
8.8.4
8.9
8.9.1
8.9.1.1
8.9.1.2
8.9.1.3
8.9.1.4
8.9.1.5
8.9.1.6
8.9.1.7
8.9.1.8
8.9.1.9
8.9.1.10
8.9.2
8.9.3
8.9.4
8.9.5
8.9.6
8.9.7
8.9.8
8.9.9
8.9.10
8.9.10.1
8.10
8.11
8.11.1
8.11.2
8.11.3
8.11.3.1
8.11.3.2
8.11.3.3
8.11.3.4
8.11.4
8.11.4.1
8.11.4.2
8.11.4.3
8.11.4.4
8.11.5
8.11.5.1
8.11.5.2
8.11.5.3
8.11.5.4
8.11.6
8.11.6.1
8.11.6.2
8.11.6.3
8.11.6.4
8.11.7
8.11.7.1
Fetal Karyotyping
160
Extended Banding Chromosome Studies
160
Innovation in Invasive Testing: Rapid Aneuploidy Detection Method 160
Microarrays: An Alternative for Karyotyping
161
Rapid Aneuploid Detection by QF-PCR
161
Principles of QF-PCR
161
Fluorescence in situ Hybridization (FISH) 162
The Format of FISH Test Result 163
Commonly Used FISH-Based Tests
164
Microdeletions/Microduplications Detectable by FISH
165
Types of FISH Probes and their Functions 165
Microarray-Based Comparative Genomic Hybridization (array-CGH) 166
Advances in Prenatal Testing: The Power to Know Sooner
167
Noninvasive Prenatal Tests (NIPTs): An overview of Tests and Technologies 168
Harmony Test 168
InformaSeq
170
Panorama Test 170
Prena Test
171
NIFTY Test
172
IONA Test
172
Verifi Test
174
MaterniT GENOME Test 175
MaterniT21 PLUS Test 176
HerediT UNIVERSAL Carrier Screen
177
Comparison of MaterniT21 PLUS, Verifi, Harmony and Panorama Tests
177
U.S. Patents for NIPTs by Company in the U.S.
178
Selected Issued Patents of NIPTs 178
Assignees of Major U.S. Patents and their Current Licensees 179
Global Availability of NIPTs
180
Cost Effectiveness of NIPTs
181
Strategies to be adopted for Clinical Implementation of NIPT for all Pregnancies
Integration of NIPT into Healthcare System: Patient-Directed Model 182
Controversial Advertisements of NIPT
183
FDA Regulatory Loophole
184
Tandem Mass Spectrometry (MS/MS) in Newborn Screening 184
Fetal Ultrasound in Prenatal Screening
185
Types of Fetal Ultrasound Exams 185
Best Obstetric and Gynecological Ultrasounds in the Market 185
Best Premium Fetal Ultrasound Machines 186
Philips Epiq 7 186
GE Voluson E8 187
GE Voluson E10 187
Samsung UGEO WS80A 188
High-End Systems
188
Philips Epiq 5 188
Philips Affinity 70
189
GE Voluson E6 189
GE Voluson S8 190
Midrange Systems
190
Philips Affinity 50
190
GE Voluson S6 191
Samsung AccuVix A30 191
Philips ClearVue 650
191
Economy Systems
192
Philips ClearVue 550
192
GE Logiq P5
192
Samsung H60 193
Alpinion Ecube 7
193
Portable Systems 193
GE Voluson i 194
182
8.11.7.2
9.0
9.1
9.1.1
9.2
9.3
9.4
9.4.1
9.5
9.6
9.7
10.0
10.1
10.2
10.3
10.4
11.0
11.5.1
11.5.2
11.5.2.1
11.5.2.2
11.5.2.3
11.5.2.4
11.5.2.5
11.5.3
11.5.4
11.5.5
11.6
11.6.1
11.6.2
11.6.3
11.6.4
11.7
11.8
11.8.1
11.8.2
11.9
10.11
12.0
12.1
12.2
12.2.1
12.3
12.3.1
12.3.2
12.4
12.4.1
12.5
12.6
12.6.1
12.7
12.7.1
12.7.2
12.7.3
12.7.3.1
12.7.3.2
12.7.3.3
12.7.3.4
12.8
12.8.1
Samsung UGEO HM70A 194
Prenatal Screening and Diagnosis: Market Overview 195
Global Market for Fetal Ultrasound 195
Market Leaders in Fetal Ultrasound 196
Global Market for Prenatal MRI Screening 197
Global Market for Maternal Serum Screening Tests 199
Global Market for Non-Invasive Prenatal Tests (NIPT) using cffDNA 200
Global Market for NIPTs by Product
202
Global Market for Prenatal Diagnostic Tests 203
Global Market for Newborn Screening for Genetic Diseases 204
Global Market for Pre-implantation Genetic Screening/Diagnosis (PGS/PGD)
Other Genetic Testing-Related Markets: A Brief Overview
207
Emerging Trends in Molecular Diagnostics Market 207
Emerging Trends in Liquid Biopsy Market 208
Emerging Trends in Personalized Medicine Diagnostics Market
209
Emerging Trends in in vitro Diagnostics (IVD) Market
210
Market SWOT and Strategy Analysis
212
Strategies of Major Players in Prenatal Screening Industry
212
Acquisition Activities in Prenatal Screening Industr5y
212
Acquisition of BlueGenome by Illumina
212
Illumina’s Acquisition of Verinata Health 212
Eurofin’s Joint Venture with Emory Genetics Laboratory
212
Roche’s Acquisition of Ariosa Diagnostics 212
Cooper Surgical’s Acquisition of Reprogenetics
212
Market Drivers of Prenatal Screening
213
Market Restraints
213
Future of Prenatal Screening
213
Legislation Mandating Newborn Screening by Geography
213
Newborn Screening Programs in Americas 214
Newborn Screening Programs in Asia/Pacific
214
Newborn Screening Programs in Europe
214
Newborn Screening Programs in Middle East and Northern Africa (MENA)
Ethical Voices against Problematic Applications of NIPT and NIPD
215
Clinical Implementation of NIPTs 216
Implementation of NIPT in Developed Countries
216
Implementation of NIPTs in Developing and Under-Developed Countries
Adoption Rates for Different Prenatal Testing in the U.S.
217
Reimbursement for NIPTs 217
Company Profiles
218
23andMe Inc.
218
Abbott Laboratories
219
ARCHITECT AFP Assay 219
Abbott Molecular Inc.
219
AneuVysion
219
Cystic Fibrosis Genotyping Assay 220
Abcam plc
220
hCG Human ELISA Kit 220
AB Sciex LLC 220
Adaltis S.r.l
221
CLIAgen Free Beta-hCG Kit
221
Adaptive Biotechnologies Corp. 221
ImmunoSEQ Platform
221
ClonoSEQ
222
Pipeline 222
Quantifying Tumor Infiltration Lymphocytes in Solid Tumors 222
Measuring Immune Reconstitution Post Transplant 222
Diagnosing Cutaneous T-Cell Lymphoma (CTCL) 222
Therapeutics
222
Affymetrix Inc. 223
Microarray Solutions
223
205
215
216
12.9
Agena Biosciences Inc. 224
12.9.1 MassARRAY System
224
12.10 Agilent Technologies Inc. 225
12.10.1 SureScan Microarray Scanner
225
12.10.2 OneSeq 225
12.11 Ambry Genetics Corp.
225
12.11.1 Clinical Diagnostic Tests 225
12.12 Analogic Corp. 227
12.12.1 Flex Focus 500 227
12.12.1 SonixTouchQ+ 227
12.12.3 SonixSP Q+
227
12.13 Ariosa Diagnostics Inc. 228
12.13.1 Harmony Test 228
12.14 Ansh Labs
228
12.14.1 picoPAPP-A ELISA Kit 228
12.14.2 Inhibin A ELISA Kit
228
12.15 Appistry Inc.
229
12.15.1 GenomePilot
229
12.15.3 Variant Annotation and Analysis Suite
229
12.15.4 CloudDx Translational 229
12.15.5 CloudDx Clinical
229
12.16 ARUP Laboratories
230
12.16.1 Prenatal Screening and Diagnosis 230
12.16.2 Next-Generation Sequencing (NGS)
230
12.16.3 Noninvasive Prenatal Test for Aneuploids 230
12.17 AssureRx Health Inc.
231
12.17.1 GeneSight Psychotropic 231
12.17.2 GeneSight Analgesic
231
12.17.3 GeneSight ADHD
231
12.17.4 GeneSight MTHFR
231
12.18 Asuragen Inc.
232
12.18.1 AmplideX FMR1 PCR 232
12.18.2 AmplideX FMR1 mPCR 232
12.18.3 AmplideX Controls
232
12.18.4 Quantidex Pan Cancer Kit 232
12.18.5 Quantidex BCR/ABL1 Quant Kit 232
12.18.6 Quantidex DNA Assay 233
12.18.7 Signature Technology
233
12.18.8 Signature KRAS Mutations
233
12.18.9 Signature BRAF Mutations
233
12.18.10 Signature LTx v2.0
233
12.18.11 Signature NPM1 Mutations
233
12.19 Ariosa Diagnostics Inc. 234
12.19.1 Harmony Test 234
12.20 Athena Diagnostics Inc. 234
12.21 AutoGenomics Inc.
235
12.21.1 INFINITI System
235
12.22 Base4 Innovation Ltd.
235
12.22.1 Microdroplet Sequencing 236
12.23 Beckman Coulter Inc.
236
12.23.1 SPRIworks System I for Illumina Genome Analyzer 236
12.23.2 SPRIworks HT for Illumina NGS Platform 236
12.23.3 SPRIselect Reagent Kit 236
12.23.4 Automated Sample Preparation
237
12.23.5 Genomic Services
237
12.23.6 Access Total Beta-hCG Reagent 237
12.23.7 Access Inhibin A Assay 237
12.24 Berry Genomics Co., Ltd. 237
12.24.1 Bambni Test
238
12.25 Bina Technologies Inc.
238
12.25.1
12.25.2
12.26
12.27
12.28
12.28.1
12.29
12.29.1
12.29.2
12.30
12.30.1
12.30.2
12.31
12.31.1
12.31.2
12.32
12.32.1
12.32.2
12.32.3
12.33
12.34
12.35
12.35.1
12.36
12.37
12.37.1
12.38
12.38.1
12.38.2
12.39
12.39.1
12.39.2
12.40
12.40.1
12.41
12.42
12.42.1
12.42.2
12.42.3
12.43
12.44
12.44.1
12.44.2
12.44.3
12.45
12.45.1
12.45.2
12.46
12.47
12.47.1
12.48
12.48.1
12.49
12.49.1
12.50
12.50.1
12.50.2
12.50.3
12.51
12.52
Bina RAVE
238
Bina AAiM
238
Bio-Rad (Israel) Laboratories Inc. 239
BGI
239
Blueprint Genetics Oy
240
Services
240
Boreal Genomics Inc.
240
OnTarget Mutation Detection System
241
Aurora Platform 241
Cambridge Epigenetix Ltd.
241
TrueMethyl Seq Kit
241
TrueMethyl Array
242
Caris Lifesciences
242
ADAPT Biotargeting System
242
Caris Molecular Intelligence
242
CeGaT GmbH 243
NGS Service
243
ADME Research Panel 243
Forschungsexom 243
Centogene AG 244
Chromsystems Instruments & Chemicals GmbH
Chronix Biomedical Inc. 245
Technology
245
Claritas Genomics Inc.
245
CLC bio A/S
248
Products
248
Combimatrix Corp.
249
CombiSNP Array for Prenatal Diagnosis 249
CombiPGS
249
Contec Medical Systems Co., Ltd. 255
CMS600P B-Ultrasound Diagnostic System 255
CMS600B3 B-Ultrasound Diagnostic System
Coriell Life Sciences Inc. 255
GeneDose
255
Correlagen Diagnostics Inc.
256
Counsyl Inc.
258
Family Prep Screen
258
Informed Pregnancy Screen
258
Inherited Cancer Screen 258
Courtagen Life Sciences Inc.
259
Creative Diagnostics
259
Alpha-Fetoprotein, AFP ELISA Kit
259
hCG ELISA Kit 260
Human Free Estriol ELISA Kit
260
Cynvenio Biosystems Inc. 260
LiquidBiopsy 260
ClearID 260
Diagnostic Automation/Cortez Diagnostics Inc.
Demeditec Diagnostics GmbH
261
Estriol, Free/Uncojugated ELISA 261
DRG International Inc.
262
DRG PAPP-A ELISA
262
DNA Electronics Ltd.
262
Genalysis
262
DNA Link Inc. 263
Services
263
DNAGPS
264
AccuID 264
DNAnexus Inc. 264
Eagle Biosciences Inc.
265
244
255
261
12.52.1
12.52.2
12.53
12.53.1
12.53.2
12.54
12.54.1
12.54.2
12.55
12.55.1
12.55.2
12.55.3
12.55.4
12.55.5
12.56
12.56.1
12.57
12.57.1
12.58
12.58.1
12.58.2
12.58.3
12.58.4
12.59
12.59.1
12.60
12.60.1
12.60.2
12.60.3
12.60.4
12.60.5
12.60.6
12.60.7
12.60.8
12.61
12.61.1
12.62
12.63
12.64
12.64.1
12.64.2
12.64.3
12.65
12.65.1
12.66
12.66.1
12.66.2
12.66.3
12.67
12.67.1
12.67.2
12.67.3
12.67.4
12.68
12.69
12.69.1
12.70
12.70.1
12.70.2
12.71
Alport Syndrome Kit
265
Free Beta-hCG ELISA 265
Eagle Genomics Ltd.
265
EagleCore
266
EagleNsembl
266
Enzymatics Inc. 266
Reagents
266
SPARK DNA Sample Preparation Kit
266
Esoate SpA
267
MyLabGamma 267
MyLab GOLD Platform 267
MyLab 50
267
MyLab 40
267
MyLab 25Gold 267
Eurofins MWG Operon Inc.
268
Products and Services
268
Exiqon A/S
269
Products and Services
269
Fakuda Denshi Co., Ltd. 270
UF-400AX
270
UF-550XTD
270
UF-760AG
271
UF-870AG
271
GATC Biotech AG
272
Sanger Sequencing
272
GE Healthcare Ltd.
272
VScan 273
VScan with Dual Probe 273
Logiq P5
273
Logiq P6
273
GE Venue 50
273
GE Venue 40
273
Logiq S8
273
Logiq E9
274
GenapSys Inc. 274
GENIUS
274
Gene by Gene Ltd.
274
Genection Inc. 275
GeneDx Inc.
276
Cytogenetics and Biochemical Tests
276
Deletion/Duplication Analysis
276
Carrier Mutation-Specific Testing 277
GenePeeks Inc. 277
Matchright Technology 277
Genesis Genetics 278
GeniSeq24
278
UltraPGD
278
ArrayCGH
278
Genetadi Biotech S.L.
279
AMNIOCHIP 279
FERTICHIP
279
PRENATAL GENE
279
NEONATAL-ONE
280
Genoma Group Srl
280
Genomed AG
280
Aneufast
281
GenPath Diagnostics
281
InheriGen, InheriGen Plus and InheriGen Tx
Prenatal Tests 281
Genway Biotech Inc.
282
281
12.72 Good Start Genetics Inc. 282
12.72.1 EmbryVu
282
12.73 Hitachi Medical Systems America Inc.
282
12.73.1 Arietta 70
283
12.73.2 ProSound Alpha 7
283
12.73.3 Noblus 283
12.73.4 ProSound F37 283
12.74 Hologic Inc.
283
12.74.1 InPlex CF Molecular Test 283
12.74.2 Rapid fFN Test 284
12.75 Illumina Inc.
284
12.75.1 The Verifi Prenatal Test 284
12.76 INEX Innovations Exchange Pte Ltd.
285
12.76.1 iGene 285
12.76.2 FlashFISH
285
12.77 Invitae Corp.
286
12.78 Laboratory Corporation of America Inc.
286
12.78.1 Services
286
12.79 LifeCodexx AG 287
12.79.1 Prena Test
287
12.80 Monobind Inc. 287
12.80.1 Fertility VAST Panel: HCG, FSH, LH, SPRL
12.80.2 PAPP-A Test
288
12.81 Multiplicom NV 288
12.81.1 Clarigo 288
12.82 Myriad Genetics 288
12.83 Natera Inc.
289
12.83.1 Panorama Prenatal Screen 289
12.83.1.1
Accuracy of Panorama Test
289
12.83.1.2
Minimal False Negatives in Panorama
12.83.2 Horizon Carrier Screening
290
12.83.3 Spectrum Preimplantation Test
291
12.83.4 Natera’s 24-chromosome PGS
292
12.83.5 Anora Miscarriage Test 292
12.83.6 Prenatal Paternity Test 292
12.84 Natus Medical Inc.
292
12.84.1 ABaer 293
12.84.2 Algo 5 293
12.84.3 Algo 3i 293
12.84.4 AuDX 293
12.84.5 Echo-Screen III 293
12.85 NewGene Ltd. 294
12.85.1 Hereditary Disorders
294
12.85.2 Alport Syndrome
294
12.85.3 Aortopathy Panel
294
12.85.4 RASopathy Gene Panel 295
12.85.5 Familial Hypercholesterolaemia 295
12.86 NIPD Genetics Ltd.
295
12.86.1 VERACITY Test (NIPT) 295
12.87 Oxford Gene Technology (OGT) 296
12.87.1 SureSeq NGS Library Preparation Kit
296
12.87.2 CytoSure Embryo Screen Array 296
12.87.3 Cytocell FISH Probes
296
12.87.4 CytoSure Embryo Screen Array 296
12.87.5 CytoSure Aneuploidy Array
296
12.87.6 CytoSure Chromosome X Arrays 297
12.88 Parabase Genomics Inc. 297
12.88.1 NewbornDx Test 297
12.89 Pathway Genomics Corp. 298
12.89.1 Carrier Screening
298
288
290
12.90 PerkinElmer Life and Analytical Sciences Inc.
298
12.90.1 DELFIA Xpress PIGF Assay
298
12.90.2 DELFIA Xpress PAPP-A Kit
298
12.90.3 AutoDELFIA PAPP-A Kit
299
12.90.4 StepOne Newborn Screens
299
12.91 Premaitha Health PLC
299
12.91.1 IONA Test
299
12.92 Progenity Inc.
300
12.92.1 nxtPanel Test 300
12.92.2 Verifi Test
300
12.93 Qiagen N.V.
301
12.93.1 Next-Generation Sequencing (NGS)
301
12.93.2 Target Enrichment Solutions
301
12.93.3 Library Construction
302
12.94 Quest Diagnostics Inc.
302
12.94.1 QNatal Advanced
302
12.94.2 Inhibin A
302
12.95 Ravgen Inc.
303
12.95.1 Prenatal Downs Syndrome Testing 303
12.95.2 Single Gene Disorder Testing
303
12.96 Recombine Inc. 303
12.96.1 CarrierMap
303
12.97 Reproductive Genetics Institute Inc.
304
12.98 Reprogenetics Laboratories
304
12.98.1 Array CGH (aCGH)
304
12.98.2 Single Gene Disorder Testing
304
12.99 Sebia Inc.
305
12.100 Sequenom Inc. 305
12.100.1 MaterniT GENOME Test 305
12.100.1.1
Sensitivity and Specificity of MaterniT GENOME Test
12.100.2 MaterniT21 PLUS
307
12.100.2.1
Sensitivity and Specificity of MaterniT21 PLUS
307
12.100.3 HerediT UNIVERSAL Carrier Screen
307
12.100.4 VisibiliT Prenatal Test
308
12.100.5 HerediT Cystic Fibrosis Carrier Screen
308
12.100.5.1
Clinical Data for HerediT 308
12.100.6 SensiGene Fetal RHD Genotyping 309
12.100.7 NextView Prenatal Diagnostic Tests
309
12.101 SeraCare Life Sciences Inc.
310
12.101.1 Seraseq Trisomy 21 Aneuploidy Reference Material 310
12.102 Siemens Healthcare
311
12.102.1 Acuson S2000 311
12.102.2 Acuson X700
311
11.102.3 Acuson X600
311
12.102.4 Acuson X300 PE 311
12.102.5 Acuson X150
312
12.102.6 Acuson Antares 312
12.102.7 Acuson P300
312
12.103 Sophia Genetics SA
312
12.103.1 Clinical Genomic Modules
312
12.104 SpOtOn Clinical Diagnostics Ltd. 313
12.104.1 Newborn Screening
313
12.104.2 Ante-Natal Testing
313
12.105 Stra Biotech GmbH
313
12.106 Sygnis AG
314
12.106.1 TruePrime Single Cell WGA Kit 314
12.106.2 TruePrime WGA Kit
314
12.106.3 TruePrime RCA Kit
314
12.106.4 SunScript Reverse Transcriptase RNaseH+ and RNaseH- Kits 314
12.106.5 SensiPhi/QualiPhi
314
306
12.107 SynapDx Corporation
315
12.107.1 ASD Diagnosis 315
12.108 Thermo Fisher Scientific Inc.
315
12.108.1 Thermo Fisher’s Brands 315
12.109 Transgenomic Inc.
316
12.109.1 Technology Suite 316
12.109.2 MX-ICP Technology
317
12.109.3 ICEme Kit
317
12.109.4 Other Products 317
12.110 Trivitron Healthcare Private Ltd. 317
12.111 Trovagene Inc. 318
12.111.1 PCM BRAF V600E Mutation Detection Test
318
12.111.2 PCM KRAS Mutation Detection Test
318
12.111.3 PCR EGFR Mutation Detection Test
319
12.111.4 HPV HR Detection Test 319
12.112 Tute Genomics Inc.
319
12.112.1 Tute Platform
320
12.113 Warp Drive Bio LLC
320
12.113.1 Wrap’s New Approach
320
12.113.2 Chemomemes 320
12.113.3 Genomic Search Engine 320
12.114 ZS Genetics Inc. 321
12.114.1 3G Sequencing 321
12.115 Zymo Research Corporation
321
12.115.1 DNA Methylation Products
321
12.115.1.1
Bisulfite Conversion
321
12.115.1.2
Methylated DNA Standards
322
12.115.1.3
DNA Methyltransferases 322
12.115.1.4
5-mC ELISA
322
12.115.1.5
5-mC Antibodies and Immunoprecipitation 322
11.115.1.6
Region-Specific DNA Methylation Analysis 322
12.115.1.7
Global 5-mC Quantification
322
12.115.1.8
Genome-wide 5-mC Analysis
323
12.115.2 DNA Purification Products
323
12.115.2.1
DNA Clean-up 323
12.115.2.2
Plasmid DNA Purification 323
12.115.2.3
Genomic DNA 323
12.115.3 Microbial and Environmental DNA Isolation324
12.115.4 DNA/RNA Co-Purification
324
12.115.5 Sample Collection and Stabilization
324
12.115.6 DNA Ladders
324
12.115.7 Enzymes
324
12.115.8 High-Throughput/Automated Isolation
325
12.115.9 DNA Analysis Kits
325
12.115.10
Other Products 325
INDEX OF FIGURES
Figure 1.1: Summary of Prenatal Screening, Prenatal Diagnosis, Newborn Screening and PGS/PGD Markets,
Through 2021
22
Figure 2.1: Risk of Down syndrome and All Chromosomal Abnormalities Due to Maternal Age 26
Figure 2.2: Risk of Miscarriage with Increasing Maternal Age 27
Figure 2.3 Increased Rate of Cesarean Section with Increasing Maternal Age
28
Figure 2.4: Risk of Gestational Diabetes with Advanced Maternal Age 29
Figure 2.5: Risk of Placenta Previa with Advanced Maternal Age
30
Figure 2.6: Increasing Rates for First Births to Older Women in the U.S.
31
Figure 2.7: First Birth Rates for 35-39 Aged Women by Race in the U.S.
32
Figure 2.8: Pre-Existing Chronic Diseases among Women of Reproductive Ages in the U.S.
39
Figure 2.9: Chronic Disease Risk Behaviors and Risk Factors among Women of Reproductive Age in the U.S.
39
Figure 2.10: Prevalence of Preeclampsia during Pregnancy by Race/Ethnicity in the U.S. 41
Figure 2.11: Prevalence of Preeclampsia during Pregnancy by Maternal Age in the U.S. 41
Figure 2.12: Prevalence of Gestational Diabetes by Maternal Age in the U.S.
43
Figure 2.13: Prevalence of Gestational Diabetes by Maternal Race/Ethnicity in the U.S. 43
Figure 2.14: Causes of Preterm Labor
44
Figure 2.15: Prevalence of Preterm Births in the U.S. by Stage 46
Figure 2.16: Prevalence of Preterm Births in the U.S. by Race/Ethnicity, 2013 47
Figure 2.17: Prevalence of Preterm Births in the U.S. by Plurality of Birth, 2013 48
Figure 2.18: Prevalence of Preterm Births in the U.S. by Maternal Age, 2013
49
Figure 2.19: Prevalence of Multiple Births in the U.S. 49
Figure 3.1: Autosomal Dominant Faulty Gene Inheritance When One Parent is a Carrier 57
Figure 3.2: Autosomal Dominant Faulty Gene Inheritance When Both the Parents are Carriers
58
Figure 3.3: Percent of Patients with Sweat Chloride Test Reported in the U.S. Registry, 1988-2013 59
Figure 3.4: Age at CF Diagnosis for All People Reported in the U.S. Registry, 2013
60
Figure 3.5: Distribution of Race/Ethnicity among People with CF in the U.S.
60
Figure 3.6: Percent of New CF Diagnosis in Newborn Screening in the U.S., 1990-2013 61
Figure 3.7: Autosomal Recessive Inheritance with Both the Parents being Carriers
68
Figure 3.8: Autosomal Recessive Inheritance with Carrier Mother and Non-Carrier Father 69
Figure 3.9: Autosomal Recessive Inheritance from Homozygous Recessive Mother and Carrier Father
69
Figure 3.10: Autosomal Recessive Inheritance from Both the Parents being Affected
70
Figure 3.11: Inheritance Pattern of Sex-Linked Dominant Disorder with Mother being affected and Father being
a Non-Carrier
75
Figure 3.12: X-Linked Recessive Inheritance with a Carrier Mother and Non-Carrier Father
81
Figure 3.13: X-Linked Recessive Inheritance with Normal Mother and Affected Father 81
Figure 3.14: Prevalence of Down syndrome by Mother’s Age in the U.S.
88
Figure 3.15: Prevalence of Trisomies in the U.S.
93
Figure 3.16: Relative Frequencies of Different Abnormalities in Chromosomally Abnormal Spontaneous
Abortions
94
Figure 3.17: Maternal Age and Chromosomal Abnormalities Detected at Amniocentesis 96
Figure 5.1: Genetic Disorders (%) Detectable by Prenatal Testing Methods
125
Figure 5.2: Nuchal Translucency as Seen in an Ultrasound Scan
126
Figure 5.3: The Amniocentesis Procedure 128
Figure 5.4: Transabdominal CVS Test
129
Figure 5.5: Transvaginal CVS Test 129
Figure 5.6: Scheme for Isolating Fetal Cells to be used for Noninvasive Prenatal Genetic Diagnosis
134
Figure 7.1: Indications for PGD
146
Figure 8.1: Markings on a hCG Test Strip 156
Figure 8.2: Procedure of the Test (hCG)
157
Figure 8.3: Interpretation of hCG Result
157
Figure 8.4: The Fetal Karyotype Showing Down Syndrome 160
Figure 8.5: Peak Heights Indicating Aneuploidy in QF-PCR Study
162
Figure 8.6: Diagrammatic Representation of Steps Involved in FISH Test
163
Figure 8.7: FISH Test Showing Chromosomal Deletion
163
Figure 8.8: Steps involved in array-CGH
166
Figure 8.9: History of Innovation in NIPTs from 2011 to 2015 168
Figure 8.10: Detection Rate of Harmony Test Compared with Traditional Maternal Serum Tests 169
Figure 8.11: Global Availability of NIPTs 180
Figure 8.24: Patient-Directed Model of Integrating NIPTs into Healthcare Setting
183
Figure 9.1: Global Market for Prenatal Screening by Ultrasound, Through 2021 195
Figure 9.2: Global Market for Fetal Ultrasound Screening by Geography, Through 2021 196
Figure 9.3: Global Fetal Ultrasound Market Share by Company, 2014 197
Figure 9.4: Global Market for Prenatal Screening by MRI, Through 2021
198
Figure 9.5: Global Market for MRI Prenatal Screening by Geography, Through 2021
198
Figure 9.6: Global Market for Maternal Serum Screening Tests by Geography, Through 2021
200
Figure 9.7: Global Market for NIPT, Through 2021 201
Figure 9.8: Global Market for NIPT by Geography, Through 2021
201
Figure 9.9: Global Market for NIPTs by Product
202
Figure 9.10: Global Market for Prenatal Diagnostic Tests, Through 2021
203
Figure 9.11: Global Market for Newborn Screening for Genetic Diseases, Through 2021 204
Figure 9.12: Global Market for Newborn Screening by Technology, Through 2021
205
Figure 9.13: Global Market for Pre-implantation Genetic Diagnosis (PGD), Through 2021
Figure 9.14: Global Market for Pre-implantation Genetic Diagnosis (PGD), Through 2021
Figure 10.1: Global Market for Molecular Diagnostics, Through 2021 208
Figure 10.2: Global Liquid Biopsy Market, Through 2021
209
Figure 10.3: Global Personalized Medicine Diagnostics Market, Through 2021 210
Figure 10.4: Global Market for IVD, Through 2021 211
Figure 12.1: Comparison of False Negative Rates
290
Figure 12.2: Sensitivity and Specificity of MaterniT GENOME Test
306
206
206
INDEX OF TABLES
Table 1.1: Summary of Prenatal Screening, Prenatal Diagnosis, Newborn Screening and PGS/PGD Markets,
Through 2021
22
Table 2.1: Risk of Down syndrome and Chromosomal Abnormalities Due to Maternal Age
26
Table 2.2: Maternal Age and Pregnancy Loss Rate 27
Table 2.3: Risk of Cesarean Section with Increasing Maternal Age
28
Table 2.4: Risk of Gestational Diabetes with Advanced Maternal Age 28
Table 2.5: Risk of Placenta Previa with Advanced Maternal Age
29
Table 2.6: Increasing Rates (per Thousand Women) for First Births to Older Women in the U.S. 30
Table 2.7: First Birth Rates for 35-39 Aged Women by Race in the U.S. 31
Table 2.8: Maternal and Fetal Concerns Due to Pre-Existing Medical Issues
33
Table 2.9: Pregnancy Outcome in Women with Pre-Existing Renal Problems
33
Table 2.10: Hypothyroidism-Related Adverse Effects During Pregnancy
34
Table 2.11: Risks Associated with Pregnancy in Obese Women
35
Table 2.12: Pregnancy Complications in Asthmatic Women 35
Table 2.13: Pregnancy-Related Complications and Neonatal Outcomes in Women with Epilepsy 36
Table 2.14: Maternal and Fetal Complications in Women with Autoimmune Diseases
37
Table 2.15: Complications Due to Hemoglobinopathies in Pregnancy 38
Table 2.16: Prevalence of Gestational Diabetes in the U.S.
42
Table 2.17: Countries with Higher and Lower Rates of Preterm Births 45
Table 2.18: Prevalence of Preterm Births in the U.S. by Stage 46
Table 2.19: Prevalence of Preterm Births in the U.S. by Race/Ethnicity 47
Table 2.20: Prevalence of Preterm Births in the U.S. by Plurality of Birth, 2013 48
Table 2.21: Prevalence of Preterm Births in the U.S. by Maternal Age 48
Table 2.22: Related Complications of Placenta Previa 50
Table 2.23: Mode of Delivery for Beech Presentation 50
Table 2.24: Perinatal Outcome due to Meconium Stained Liqor
51
Table 2.25: Pregnancy Outcome due to Polyhydramnios
51
Table 2.26: Causes of Fetal Growth Restrictions
52
Table 2.27: Prevalence of Congenital Cardiovascular Defects in Fetuses in the U.S.
53
Table 3.1: Worldwide Prevalence of Huntington Disease by Selected Country 55
Table 3.2: Prevalence of 25 Most Common CFTR Mutations in the U.S.,2013 62
Table 3.3: Molecular Genetic Testing Used in Canavan Disease
63
Table 3.4: Incidence of SCD in the U.S.
66
Table 3.5: Red Blood Cell Indices in Beta-Thalassemia
67
Table 3.6: Molecular Genetic Testing Used in Beta-Thalassemia
68
Table 3.7: Chances of Inheriting a Single Gene Disorder
70
Table 3.8: More Common Recessive Disease Traits in Selected Ethnic Groups 71
Table 3.9: A Comprehensive List of Genetic Disorders
71
Table 3.10: Turnaround Time and Average Cost for Hemophilia Genetic Testing 78
Table 3.11: Incidence of Chromosomal Abnormalities
83
Table 3.12: Karyotypes Commonly Associated with Klinefelter Syndrome
84
Table 3.13: Features of Turner Syndrome in Different Age Groups
85
Table 3.14: Some Complications of Down syndrome 86
Table 3.15: Incidence of Down syndrome by Maternal Age
88
Table 3.16: Developmental Delay in Down syndrome Children
89
Table 3.17: Frequently Observed Anomalies in Babies with Edward’s Syndrome 90
Table 3.18: Common Clinical Features of Trisomy 13 91
Table 3.19: Congenital Anomalies Associated with Triploidy 92
Table 3.20: Relative Frequencies of Different Abnormalities in Chromosomally Abnormal Spontaneous
Abortions
94
Table 3.21: Maternal Age-Related Frequency of Aneuploid Fetuses Detected Prenatally 94
Table 3.22: Clinical Features of Babies with Common Autosomal or Sex Chromosome Aneuploidy
95
Table 3.23: Maternal Age and Chromosomal Abnormalities Detected at Amniocentesis 95
Table 3.24: Sensitivity and Specificity of Maternal Serum and Ultrasound Tests 96
Table 3.25: Common Autosomal Deletions, Resulting Syndromes and Clinical Features 97
Table 3.26: Common Autosomal Microdeletion Syndromes 100
Table 3.27: Commonly Encountered Problems in Prader-Willi Syndrome
102
Table 3.28: Testings Used in Prader-Willi Syndrome 102
Table 3.29: Molecular Genetic Testing Used in the 22q 11.2 Deletion Syndrome 106
Table 3.30: Autosomal Duplication Syndromes
107
Table 3.31: Molecular Genetic Testing Used in Beckwith-Wiedemann Syndrome
108
Table 3.32: Molecular Genetic Testing Used in Charcot-Marie-Tooth Neuropathy Type 1 (CMT1) 109
Table 5.1: Major Prenatal Screening Tests during the First and Second Trimesters
113
Table 5.2: Other Routine and Non-Routine Prenatal Screening Tests
114
Table 5.3: hCG Levels from Date of Conception to 40th Week 114
Table 5.4: Selected β-hCG Kits and Manufacturers 115
Table 5.5: Selected PAPP-A Kits and Manufacturers 115
Table 5.6: Selected MSAFP Test Kits and Manufacturers
116
Table 5.7: Selected uE3 Test Kits 116
Table 5.8: Selected Inhibin-A Test Kits
117
Table 5.9: Selected Hexosaminidase Test Kits
117
Table 5.10: Comparison of the Four Maternal Serum Screening Analyte Patterns 118
Table 5.11: The Five Popular Commercially Available NIPTs 118
Table 5.12: Sensitivity and Specificity of NIPT
119
Table 5.13: Prenatal Screening/Diagnostic Applications of cffDNA
119
Table 5.14: Time of Availability of cffDNA in Maternal Plasma
119
Table 5.15: The Cost of NIPT Testing by Country/Region
120
Table 5.16: Cost of NIPTs by Product
120
Table 5.17: History of Aneuploid Screening 121
Table 5.18: NIPT Methods for Detecting Aneuploidy 122
Table 5.19: Comparison of Amniocentesis and NIPTs 122
Table 5.20: Advantages and Disadvantages of NIPTs 123
Table 5.21: Comparison of Some Performance Criteria for the commonly used Prenatal Tests
123
Table 5.22: Comparison of NIPT Detection Rate with Traditional Screening Tests
124
Table 5.23: False Positive Rates (FPR) of NIPTs Compared with Traditional Screening Tests
124
Table 5.24: Different Applications of Ultrasound in Different Trimesters
126
Table 5.25: MRI Indications for Prenatal Screening when the Ultrasound Screen is Inadequate
127
Table 5.26: Prenatal Diagnostic Tests by Pregnancy Stage
127
Table 5.27: Comparison of CVS and Amniocentesis 130
Table 5.28: Advantages and Disadvantages of Prenatal Diagnostic Tests
131
Table 5.29: Comparison of Noninvasive Prenatal Diagnosis Using Fetal DNA and Intact Fetal Cells Isolated
from Maternal Blood
133
Table 6.1: Thirty One Core Conditions Detected During Newborn Screening
135
Table 6.2: The Combined Incidence of Amino Acidemias, Organic Acidemias and Fatty Acid Oxidation Defects
in Selected Countries
136
Table 6.3: Catyegories of Newborn Genetic Disorders
137
Table 6.4: Genetic or Metabolic Disorders Detectable by MS/MS and their Scores
138
Table 6.5: Incidence of PKU by Region
139
Table 6.6: Molecular Genetic Testing Used in Biotinidase Deficiency 143
Table 7.1: Advantages and Disadvantages of Available PGS/PGD Technologies 148
Table 7.2: Genetic Diseases Detected during PGD
148
Table 7.3: Currently Available Products for PGD Testing
153
Table 7.4: Average Cost of in vitro Fertilization and Related Procedures
154
Table 8.1: Karyotyping vs. Microarray Analysis
161
Table 8.2: The Format of FISH Test Results 164
Table 8.3: Some commonly used FISH-Based Tests 164
Table 8.4: Microdeletions/Microduplications Detectable by FISH
165
Table 8.5: FISH Probes and Functions
166
Table 8.6: Presentation Format of array-CGH Test Report
167
Table 8.7: Harmony vs. Traditional Down Syndrome Tests
168
Table 8.8: Predictive Value, Sensitivity and Specificity of InformaSeq Test
170
Table 8.9: Detection Rates of Panorama Test 171
Table 8.10: NIFTY Test Options 172
Table 8.11: Clinical Data for Iona Test
173
Table 8.12: Sensitivity and Specificity of Verfy Test 174
Table 8.13: Sensitivity and Specificity of Verify for Microdeletion Syndromes 175
Table 8.14: Comparison of Karyotyping and MaterniT GENOME Test 175
Table 8.15: Sensitivity and Specificity of MaterniT GENOME Test
176
Table 8.16: MaterniT21 PLUS Test’s Independent Validation 176
Table 8.17: The Three Panels Offered by HerediT UNIVERSAL Carrier Screen 177
Table 8.18: Comparison of MaterniT21 PLUS, Verifi, Harmony and Panorama Tests
177
Table 8.19: U.S. Patents for NIPTs by Company
178
Table 8.20: Selected Issued Patents of NIPTs
179
Table 8.21: Major U.S. Patents and Applications of Current and Emerging Prenatal Aneuploidy Tests
Table 8.22: Detection, False Positive, Uptake and Failure Rates for Prenatal Screening Types
181
Table 8.23: Cost of Different Prenatal Screens
181
Table 9.1: Global Market for Fetal Ultrasound Screening by Geography, Through 2021 196
Table 9.2: Global Fetal Ultrasound Market Share by Company, 2014 197
Table 9.3: Global Market for MRI Prenatal Screening by Geography, Through 2021
198
Table 9.4: Global Market for Maternal Serum Screening Tests by Geography, Through 2021
199
Table 9.5: Global Market for NIPT by Geography, Through 2021
201
Table 9.6: Global Market for NIPTs by Product
202
Table 9.7: Global Market for Prenatal Diagnostic Tests, Through 2021 203
Table 9.8: Global Market for Newborn Screening by Technology, Through 2021 205
Table 9.9: Global Market for Pre-implantation Genetic Diagnosis (PGD), Through 2021 206
Table 11.1: Adoption Rates for Prenatal Screening in the U.S. 217
Table 12.1: Comparison of Harmony and Other Traditional Tests
234
Table 12.2: CombiSNP Prenatal Targeted Array Disorder List 249
Table 12.3: Genetic Tests Offered by Correlagen by Gene and Disease 256
Table 12.4: GeneDx’s Cytogenetics and Biochemical Tests
276
Table 12.5: Performance of Verifi Test
284
Table 12.6: Verifi Prenatal Test Lab Partners in the U.S.
285
Table 12.7: Comparison of Prenatal Test Performance
289
Table 12.8: Comparison of False Negative Rates
290
Table 12.9: A Small Sample of Diseases Screened by Horizon Test
291
Table 12.10: Clinical Data for IONA Test 299
Table 12.11: Sensitivity and Specificity of MaterniT GENOME Test 306
Table 12.12: Sensitivity and Specificity of MaterniT21 PLUS Test
307
Table 12.13: Three Options Offered by HeridiT UNIVERSAL Carrier Screen 308
Table 12.14: Clinical Evaluation Performance of VisibiliT Prenatal Test
308
Table 12.15: CF Detection Rates for Standard and Expanded Panels
309
Table 12.16: Accuracy, Sensitivity and Specificity of SensiGene Fetal RHD
309
Table 12.17: NextView Diagnostic Test Platforms
310
180