Newborn Genetic Analysis

Fulgent Genetics Newborn Genetic Analysis

Newborn Genetic Analysis (NGA) is a highly sophisticated and sensitive genetic test that identiﬁes DNA changes that can cause infants to develop severe or life-altering conditions. Since many of these disorders are not apparent at birth, this test can help screen for these conditions, where early detection, intervention, and management are essential for the infant's overall health and quality of life.

“Newborn screening saves or improves the lives of more than 12,000 infants in the United States each year.” Genetic analysis Screens over 200 Coverage - Health Resources and Services Administration of 255 genes conditions ~99% @ 20x*

is test is designed to: Evaluate sequencing variants and whole gene deletion/duplication Screen for conditions beyond standard newborn testing Only report diagnostic ﬁndings that are clinically actionable Serve as conﬁrmatory/follow-up testing for an abnormal or inconclusive newborn screening result Early diagnosis and intervention are key in preventing or reducing severe complications

Newborn Genetic Analysis covers conditions beyond standard newborn screening

Conditions Example of Conditions Treatment Options # of Genes

Metabolic Disorders Propionic acidemia, Carnitine palmitoyltransferase II Dietary modiﬁcatioms, hormone replacement therapy, 145 (CPT II) deﬁciency, PKU, Congenital hypothyroidism surgery

Blood Disorders Thrombocytopenia, Spherocytosis, Hereditary Surveillance, transfusions hemorrhagic telangiectasia 12

Hearing Loss Connexin-related hearing loss, Pendred syndrome Hearing aids and devices 18

Congenital Heart Defect Heart defects/malformations, Marfan syndrome Surgery, increased surveillance 8

Immunodeﬁciency Agammaglobulinemia, Chronic granulomatous Prophylactic administration of antibiotics, bone marrow 22 Disorders (SCID) disease, Omenn syndrome transplantation

Pediatric Cancers Hemangioblastomas, Neuroﬁbromatosis, Increased surveillance and screening 13 Retinoblastoma, Xeroderma pigmentosum

Epilepsy Seizures, Encephalopathy Routine monitoring, anti-epileptic medication 10

Vision Loss Oculocutaneous albinism, Optic atrophy Dietary management, vision aids, reduced sun exposure 4

Other Disorders Cystic Fibrosis, Polycystic kidney disease, Spinal Surveillance, medication, transplantation 23 muscular atrophy, Usher syndrome

*Represents typical panel coverage of full-gene sequencing and deletion/duplication analysis. Technical limitations apply.

NEWBORN GENETIC ANALYSIS | FLY-NGA-V2 | 2019 1/2 Fulgent Genetics Newborn Genetic Analysis

BENEFITS OF NEWBORN GENETIC ANALYSIS Tests for over 200 conditions Has higher speciﬁcity and lower false positive rates than standard newborn screening Reduces burden of ambiguous results or complex follow-up testing Reduces “diagnostic odyssey” for aﬀected infants

Results can be used to identify potential treatment/management plans

POSSIBLE TEST RESULTS:

+ Positive: A change(s) was found in your baby’s DNA that is likely to aﬀect their health. This result may indicate necessary medical treatment or conﬁrm a diagnosis of a genetic condition in your newborn.

- Negative: Your baby’s results showed that they tested negative for an inherited genetic condition screened by this test. Although a negative result does not rule out all possibilities for having or being a carrier for a genetic condition, it does suggest that the risk is meaningfully reduced.

*Variants of uncertain clinical signiﬁcance (VUS) will not be reported.

IMPORTANT POINTS TO REMEMBER Turnaround time is 2-3 weeks from receipt of sample. This test only reports pathogenic DNA changes if they are diagnostic. This means a change was found in your baby’s DNA that is likely to affect their health. Carrier status is NOT reported. If disease-causing DNA changes are identified, parents may be carriers for the condition, and future pregnancies may be at risk. Fulgent Genetics offers additional testing to determine if the parents and other family members are at-risk to have the same DNA change. Please contact the laboratory for details. Conditions were selected with beneficence in mind. In many cases this means there is an established medical intervention. For others, however, the considered benefit is early diagnosis only, and no interventions are yet established as effective. Genetic counseling is recommended to discuss the results.

HQ | 4978 Santa Anita Ave., Suite 205, Temple City, California 91780 P | (+1) 626-350-0537 F | (+1) 626-454-1667 W | FulgentGenetics.com E | [email protected] CLIA | 05D2043189 CA | CLF 00342581 CAP | 8042697 D# | FLY-NGA-V2

BLOOD DISORDERS

Disorder Gene Beta-thalassemia HBB Congenital amegakaryocytic thrombocytopaenia MPL Congenital neutropenia ELANE, HAX1 Hemophilia B F9 Hereditary hemorrhagic telangiectasia type 1 ENG Hereditary hemorrhagic telangiectasia type 2 ACVRL1 Spherocytosis ANK1, EPB42, SLC4A1, SPTB Thrombotic thrombocytopenic purpura ADAMTS13

CANCER SYNDROMES PEDIATRIC

Disorder Gene Juvenile polyposis syndrome BMPR1A, SMAD4 Multiple endocrine neoplasia I MEN1 Neurofibromatosis type 1 NF1 Neurofibromatosis type 2 NF2 Nevoid basal cell carcinoma syndrome PTCH1 Peutz-Jeghers syndrome STK11 Retinoblastoma RB1 Von Hippel-Lindau syndrome VHL Xeroderma pigmentosum ERCC2, ERCC5, XPA, XPC

CARDIAC DISORDERS

Disorder Gene Barth syndrome TAZ Danon disease LAMP2 Heterotaxy ZIC3 Loeys-Dietz syndrome SMAD3, TGFBR1, TGFBR2 Marfan syndrome FBN1 Noonan syndrome PTPN11

EPILEPSY

Disorder Gene Benign familial neonatal seizures KCNQ2 Dravet syndrome SCN1A Early infantile epileptic encephalopathy; Benign familial infantile seizures SCN2A, SCN8A Ethylmalonic encephalopathy ETHE1 Familial infantile convulsions with paroxysmal choreoathetosis PRRT2 Pyridoxal 5'-phosphate-dependent epilepsy PNPO Pyridoxine-dependent epilepsy ALDH7A1 Tuberous sclerosis TSC1, TSC2

Newborn Genetic Analysis | Genes and Conditions | FLY-NGAGL-V2 1/5 (continued from previous page) HEARING LOSS

Disorder Gene Jervell and Lange-Nielsen syndrome KCNE1 Nonsyndromic hearing loss CDH23, GJB2, GJB6 OTOF, TECTA, TMIE TMPRSS3, TPRN, TRIOBP Pendred syndrome SLC26A4 Sensorineural hearing loss MYO15A Shah-Waardenburg syndrome SOX10 Usher syndrome 1G USH1G Usher syndrome type 1C USH1C Usher syndrome type 2A USH2A Usher syndrome IID WHRN Waardenburg syndrome PAX3

METABOLIC DISORDERS

Disorder Gene 3-beta-hydroxysteroid dehydrogenase deficiency HSD3B2 3-hydroxyacyl-CoA dehydrogenase deficiency; Congenital hyperinsulinism HADH 3-Methylcrotonyl-CoA carboxylase 1 deficiency MCCC1 3-Methylcrotonyl-CoA carboxylase 2 deficiency MCCC2 3-phosphoglycerate dehydrogenase deficiency PHGDH Abetalipoproteinemia MTTP Acrodermatitis enteropathica SLC39A4 Adrenoleukodystrophy ABCD1 Arginase deficiency ARG1 Argininosuccinic aciduria ASL Beta-ketothiolase deficiency (Alpha-methylacetoacetic aciduria) ACAT1 Biotinidase deficiency BTD Carbamoylphosphate synthetase I deficiency CPS1 Carnitine palmitoyltransferase I deficiency CPT1A Carnitine palmitoyltransferase II deficiency CPT2 Carnitine-acylcarnitine translocase deficiency SLC25A20 Central hypothyroidism and testicular enlargement IGSF1 Central hypothyroidism with thyrotropin-releasing hormone resistance TRHR Cerebral creatine deficiency syndrome GAMT, GATM Cerebral folate transport deficiency FOLR1 Cerebrotendinous xanthomatosis CYP27A1 Citrullinemia ASS1, SLC25A13 Combined pituitary hormone deficiency LHX3, PROP1 Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency CYP11B1 Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency CYP17A1 Congenital adrenal hypoplasia NR0B1 Congenital bile acid synthesis defect type 1 HSD3B7 Congenital bile acid synthesis defect type 2 AKR1D1 Congenital disorder of glycosylation 1b MPI Congenital hyperinsulinism ABCC8, HNF4A, KCNJ11 Congenital hyperinsulinism with hyperammonemia GLUD1 Congenital hypothyroidism PAX8, SLC5A5, TG THRA, TPO, TSHB, TSHR Congenital lipoid adrenal hyperplasia STAR Corticosterone methyloxidase deficiency CYP11B2

Newborn Genetic Analysis | Genes and Conditions | FLY-NGAGL-V2 2/5 (continued from previous page) METABOLIC DISORDERS

Disorder Gene Crigler-Najjar syndrome UGT1A1 Cystinosis CTNS Cytochrome P450 oxidoreductase deficiency POR Diabetes insipidus, nephrogenic AVPR2 Dihydropteridine reductase deficiency QDPR Fabry disease GLA Familial glucocorticoid deficiency MC2R Fructose-biphosphatase deficiency FBP1 Galactokinase deficiency with cataracts GALK1 Galactosemia GALE, GALT Glucose-6-phosphate dehydrogenase deficiency G6PD GLUT1 deficiency syndrome SLC2A1 Glutaric acidemia IIA ETFA Glutaric acidemia IIB ETFB Glutaric acidemia IIC ETFDH Glutaricaciduria type I GCDH Glutathione synthetase deficiency GSS Glycogen storage disease Ia G6PC Glycogen storage disease II (Pompe disease) GAA Glycogen storage disease IIIa AGL Glycogen storage disease type 0 GYS2 Glycogen storage disease type Ib SLC37A4 Glycogen storage disease VI PYGL GM1-Gangliosidosis GLB1 Hereditary fructose intolerance ALDOB HMG-CoA lyase deficiency HMGCL HMG-CoA synthase 2 deficiency HMGCS2 Holocarboxylase synthetase deficiency HLCS Homocystinuria due to cystathionine beta-synthase deficiency CBS Hypercholesterolemia LDLR Hypophosphatasia ALPL Isobutyryl-CoA dehydrogenase deficiency ACAD8 Isovaleric acidemia IVD Krabbe disease GALC Leigh syndrome SURF1 Lipoprotein lipase deficiency (LPL) LPL Lysinuric protein intolerance SLC7A7 Lysosomal acid lipase deficiency LIPA Malonyl-CoA decarboxylase deficiency MLYCD Maple syrup urine disease type Ia BCKDHA Maple syrup urine disease type Ib BCKDHB Maple syrup urine disease type II DBT Maple syrup urine disease type III DLD Medium chain acyl CoA dehydrogenase deficiency ACADM Menkes syndrome ATP7A Metachromatic leukodystrophy ARSA Methionine adenosyltransferase deficiency MAT1A Methylmalonic aciduria and homocystinuria LMBRD1, MTR, MTRR Methylmalonic aciduria cblA type MMAA Methylmalonic aciduria cblB type MMAB Methylmalonic aciduria with homocystinuria cblC type MMACHC Methylmalonic aciduria with homocystinuria cblD type MMADHC Methylmalonic aciduria, mut(0) type MUT Methylmalonyl-CoA epimerase deficiency MCEE

Newborn Genetic Analysis | Genes and Conditions | FLY-NGAGL-V2 3/5 (continued from previous page) METABOLIC DISORDERS

Disorder Gene Mitochondrial trifunctional protein deficiency HADHA, HADHB Mucopolysaccharidosis IVA GALNS Mucopolysaccharidosis type I (Hurler syndrome) IDUA Mucopolysaccharidosis type II (Hunter syndrome) IDS Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) ARSB Mucopolysaccharidosis VII GUSB N-acetylglutamate synthase deficiency NAGS Neonatal diabetes mellitus INS Neonatal hyperparathyroidism; Autosomal dominant hypocalcemia CASR Nephrogenic diabetes insipidus type II AQP2 Niemann-Pick disease type A/B SMPD1 Niemann-Pick disease type C1 NPC1 Ornithine transcarbamylase deficiency OTC Ornithine translocase deficiency; Triple H syndrome SLC25A15 Phenylketonuria PAH Pituitary hormone deficiency POU1F1 Primary hyperoxaluria type 1 AGXT Primary hyperoxaluria type 3 HOGA1 Primary hyperoxaluria type II GRHPR Propionic acidemia PCCA, PCCB Pseudohypoaldosteronism SCNN1A, SCNN1B Pyruvate kinase deficiency PKLR Sepiapterin reductase deficiency SPR Sitosterolemia ABCG5 Systemic primary carnitine deficiency SLC22A5 Tetrahydrobiopterin deficiency PCBD1, PTS Thyroid dyshormonogenesis DUOX2, DUOXA2, IYD Transcobalamin deficiency TCN2 Transient infantile liver failure TRMU Tyrosine hydroxylase deficiency TH Tyrosinemia type I FAH Tyrosinemia type II TAT Tyrosinemia type III HPD Vitamin D-dependent rickets VDR Vitamin D-dependent rickets type I CYP27B1 VLCAD deficiency ACADVL Wilson disease ATP7B

Newborn Genetic Analysis | Genes and Conditions | FLY-NGAGL-V2 4/5 (continued from previous page) IMMUNODEFICIENCY DISORDERS

Disorder Gene Bare lymphocyte syndrome RFX5, RFXANK, RFXAP Bare lymphocyte syndrome type II CIITA Chronic granulomatous disease CYBA, CYBB, NCF2 Hyper-IgE syndrome DOCK8 Immune dysregulation, polyendocrinopathy, enteropathy FOXP3 Omenn syndrome RAG1, RAG2 Severe combined immunodeficiency CD3D, CD3E, DCLRE1C IL7R, JAK3, PTPRC ZAP70, ADA, IL2RG X-linked agammaglobulinemia BTK X-linked hyper IgM syndrome CD40LG

VISION LOSS

Disorder Gene Gyrate atrophy of the choroid and retina OAT Ocular albinism type I GPR143 Oculocutaneous albinism type IV SLC45A2 Optic atrophy 1 OPA1

OTHER DISORDERS Disorder Disorder Gene Alagille syndrome JAG1 Alport syndrome COL4A3, COL4A4, COL4A5 Ataxia with isolated vitamin E deficiency TTPA Congenital insensitivity to pain with anhidrosis NTRK1 Craniometaphyseal dysplasia ANKH Crisponi syndrome CRLF1 Cystic fibrosis CFTR Dopa-responsive dystonia GCH1 Familial hemophagocytic lymphohistiocytosis PRF1 Familial Mediterranean fever MEFV Frasier syndrome WT1 Hermansky-Pudlak syndrome HPS1, HPS4 Hypophosphatemic rickets with hypercalciuria SLC34A3 Osteogenesis imperfecta COL1A1, COL1A2 Osteopetrosis TCIRG1 Polycystic kidney and hepatic disease PKHD1 Polycystic kidney disease PKD2 Spinal muscular atrophy SMN1, SMN2