Test code: 700001

CEN4GEN rapid carrier screen: Full gene sequencing panel
Test Code: 700001
Turnaround time: 4 to 8 days

What is the CEN4GEN rapid carrier screen ?
CEN4GEN uses a rapid designed molecular genomics based platform for the full gene sequencing of 107 genes, as well as SMN1 gene deletion/duplication analysis, as part of a comprehensive carrier screen for common genetic disorders in the population. A negative test result can relieve the patient in knowing that there is a reduced risk of having a child with a common genetic disorder(s). A positive test result helps the patient to pursue various reproductive options which may reduce the possibility of having an affected child with a common genetic disorder(s). Many of these disorders are treatable when detected early in newborns.

What are other CEN4GEN rapid testing options ?

  • CEN4GEN rapid supplemental newborn genetic screen (Test code: 700000)
  • CEN4GEN rapid testing for individual genetic disorders (Test codes: 700003 to 700175)

INDICATION
This test is indicated for:

  • Individuals or couples seeking to assess reproductive risk for a variety of common genetic medical conditions
  • Individuals or couples of high-risk ethnic groups or backgrounds

GENES

ABCD1, ABCD4, ACAD8, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACSF3, ADA, AHCY, ARG1, ASL, ASPA, ASS1, AUH, BCKDHA, BCKDHB, BLM, BTD, CBS, CD320, CFTR, CPT1A, CPT2, CYP21A2, DBT, DLD, DNAJC19, DUOX2, ETFA, ETFB, ETFDH, FAH, FANCC, G6PC, G6PD, GAA, GALC, GALE, GALK1, GALT, GBA, GCDH, GCH1, GJB2, GJB3, GJB6, GLA, GNMT, HADH, HADHA, HADHB, HBA1, HBA2, HBB, HCFC1, HEXA, HLCS, HMGCL, HPD, HSD17B10, IDUA, IKBKAP, IL2RG, IVD, LMBRD1, MAT1A, MCCC1, MCCC2, MCEE, MCOLN1, MLYCD, MMAA, MMAB, MMACHC, MMADHC, MTHFR, MTR, MTRR, MUT, NPC1, NPC2, OPA3, OTC, PAH, PAX8, PCBD1, PCCA, PCCB, PTS, QDPR, SLC22A5, SLC25A13, SLC25A20, SLC26A4, SLC5A5, SMN1, SMPD1, TAT, TAZ, TCN2, TG, THRA, THRB, TPO, TSHB, TSHR

METHODOLOGY

Next Generation Sequencing: In-solution hybridization of the regions encompassing full exonic gene sequences is performed on the patient’s genomic DNA for all genes except FANCC which is subjected to targeted next generation sequencing, and SMN1 is subjected to MLPA analysis only. Direct sequencing of the captured regions is performed using next generation sequencing (NGS). The patient’s gene sequences are then compared to a standard reference sequence.  All sequence variants are evaluated using current scientific data to identify pathogenic or likely pathogenic variants.

MLPA: SMN1 gene deletions were quantified by multiplex ligation polymerase chain reaction amplification (MLPA) of exons 7 and 8. Gene dosage ratios of SMN1 are calculated relative to the average of 16 reference loci and are expressed as gene dosage, and/or copy number. Diploid gene dose or 2 copies of SMN1 indicates normal (not affected) status, 1x gene dosage or 1 copy of the SMN1 gene most likely indicates carrier status and deletions (less than 0.1x) of SMN1 or 0 copies of the SMN1 gene designates affected status. The SMA component of this assay does not test for point mutations. SMN2 copy number is not assessed.

DETECTION

Next Generation Sequencing: Clinical Sensitivity: Pathogenic variants in regions other than the targeted area, including the promoter region, some mutations in the introns and other regulatory element mutations, cannot be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.

Analytical Sensitivity: ~99%.

MLPA: Deletions of the SMN1 gene are found in approximately 95% of SMA patients, but the frequency is less in the milder (type II and III) variants. Affected individuals with 0 copies of SMN1 seem to have milder form of the disease with increased copy numbers of the SMN2 gene. Deletions of the SMN1 gene are the most common pathologic mechanism for SMA, however, other gene rearrangements have been described in affected individuals, including hybrid or fusion SMN genes and deleterious point mutations in the SMN1 gene. Thus, the lack of a deletion does not necessarily rule out this diagnosis, and further testing may be required.

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types

Type: Dried Blood spots
Specimen Requirements: 5 saturated dried blood spots on filter paper
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: 5 ml
Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Saliva Specimen
Requirements: Oragene™ kit (available from CEN4GEN)
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: DNA
Requirements: 1 to 4 ug of DNA in TE buffer
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

LIST OF GENETIC DISORDERS TESTED

  • 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (Mental retardation X-linked syndromic 10 (MRXS10))
  • 2-methylbutyryl-CoA dehydrogenase deficiency (short/branched-chain acyl-CoA dehydrogenase deficiency)
  • 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMG-CoA lyase deficiency)
  • 3-hydroxyacyl-CoA dehydrogenase deficiency (M/SCHAD) (Familial hyperinsulinemic hypoglycemia type 4)
  • 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC)
  • 3-methylglutaconic aciduria (3MGA) type I (Barth Syndrome)
  • 3-methylglutaconic aciduria (3MGA) type V
  • Alpha thalassemia (Hemoglobin Disorder-Var-Hb)
  • Arginase deficiency (ARG)
  • Argininosuccinic aciduria (ASA)
  • Beta-ketothiolase (BKT) deficiency
  • Biotinidase deficiency (BIOT)
  • Bloom syndrome
  • Canavan disease
  • Carnitine palmitoyltransferase I deficiency (CPT IA)
  • Carnitine palmitoyltransferase II deficiency (CPT II)
  • Carnitine-acylcarnitine translocase (CACT) deficiency
  • Citrullinemia type I
  • Citrullinemia type II
  • Classic galactosemia type I
  • Combined malonic and methylmalonic aciduria (CMAMMA)
  • Congenital adrenal hyperplasia (CAH) (Non-classic hyperandrogenism due to 21-hydroxylase deficiency)
  • Congenital hypothyroidism (CH)
  • Cystathionine beta-synthase deficiency (homocystinuria) Hyperhomocysteinemic thrombosis
  • Cystic fibrosis (CF)
  • Fabry disease
  • Familial dysautonomia
  • Fanconi anemia, complementation group C
  • Galactokinase deficiency (galactosemia type II)
  • Galactose epimerase deficiency (galactosemia type III)
  • Gaucher disease (Types I, II, & III)
  • Glucose-6-phosphate dehydrogenase deficiency
  • Glutaric acidemia type I (GA1)
  • Glutaric acidemia type II (GA2)
  • Glycogen storage disease type Ia (GSDIa)
  • Glycogen storage disease type II (Pompe disease)
  • Holocarboxylase synthetase deficiency (MCD)
  • Homocystinuria (HCY)
  • Hypermethioninemia (MET)
  • Isobutyryl-CoA dehydrogenase (IBD) deficiency
  • Isovaleric acidemia (IVA)
  • Krabbe Disease
  • Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency (Trifunctional protein deficiency (TFP))
  • Malonyl-CoA decarboxylase deficiency (Malonic acidemia)
  • Maple syrup urine disease (MSUD)
  • Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
  • Methylmalonic acidemia (MUT)
  • Methylmalonic acidemia and homocystinuria, cblC type
  • Methylmalonic acidemia and homocystinuria, cblD type
  • Methylmalonic acidemia due to cobalamin disorder (cblA)
  • Methylmalonic acidemia due to cobalamin disorder (cblB)
  • Methylmalonic acidemia due to transcobalamin receptor defect
  • Methylmalonic acidemia with homocystinuria
  • Methylmalonic acidemia with homocystinuria, cblF type,
  • Methylmalonyl-CoA epimerase deficiency
  • Mucolipidosis type IV
  • Mucopolysaccharidosis type I (MPS I)
  • Niemann-Pick disease (Type C1)
  • Niemann-Pick disease (Type C2)
  • Niemann-Pick disease (Types A & B)
  • Non-syndromic hearing loss
  • Ornithine transcarbamylase (OTC) deficiency
  • Pendred syndrome (Congenital Hearing Loss)
  • Phenylketonuria (PKU) (Non-PKU hyperphenylalanemia (HPA))
  • Primary carnitine deficiency (CUD)
  • Propionic acidemia (PROP)
  • Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency
  • Short-chain acyl-CoA dehydrogenase (SCAD) deficiency
  • Sickle cell disease (Beta thalassemia)
  • Spinal muscular atrophy
  • Tay-Sachs disease (GM2-gangliosidosis)
  • Tetrahydrobiopterin deficiency
  • Tetrahydrobiopterin deficiency DOPA-responsive dystonia
  • Transcobalamin deficiency
  • Trifunctional protein deficiency (TFP)
  • Tyrosinemia type I
  • Tyrosinemia type II
  • Tyrosinemia type III (Hawkinsinuria)
  • Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency
  • X-linked severe combined immunodeficiency (SCID)
  • X-linked Adrenoleukodystrophy (Adrenomyeloneuropathy Addison disease (X-ALD))