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Non-syndromic Intellectual Disability (NS-ID) Sequencing Panel with CNV Detection

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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TEST METHODS

Sequencing with CNV

Test Code Test Copy GenesCPT Code Copy CPT Codes
5059 ABI2 81479,81479 Add to Order
ACSL4 81479,81479
ADGRG2 81479,81479
ADNP 81479,81479
AFF2 81479,81479
AFF3 81479,81479
AP1S2 81479,81479
ARHGEF9 81479,81479
ARID1B 81479,81479
ARX 81404,81403
ATRX 81479,81479
BCL11A 81479,81479
BDNF 81479,81479
BRWD3 81479,81479
CAPS 81479,81479
CC2D1A 81479,81479
CDH15 81479,81479
CHD2 81479,81479
CIC 81479,81479
CLCN4 81479,81479
CNTNAP2 81406,81479
CRBN 81479,81479
CTNNB1 81479,81479
CUL4B 81479,81479
DCPS 81479,81479
DDX3X 81479,81479
DEAF1 81479,81479
DLG3 81479,81479
DMBT1 81479,81479
ELP2 81479,81479
EXTL3 81479,81479
FBXO47 81479,81479
FGD1 81479,81479
FMN2 81479,81479
FOXG1 81404,81479
FTSJ1 81406,81405
GATAD2B 81479,81479
GDI1 81479,81479
GRIA3 81479,81479
GRIN1 81479,81479
GRIN2B 81479,81479
HIVEP2 81479,81479
HUWE1 81479,81479
IL1RAPL1 81479,81479
IQSEC2 81479,81479
KDM5C 81407,81479
KIRREL3 81479,81479
LAMC1 81479,81479
MAGEA11 81479,81479
MAN1B1 81479,81479
MAP3K7 81479,81479
MAPK8 81479,81479
MBD5 81479,81479
MECP2 81302,81304
MED13L 81479,81479
MED23 81479,81479
MED25 81479,81479
MEF2C 81479,81479
METTL23 81479,81479
MPDZ 81479,81479
MYT1L 81479,81479
NAA10 81479,81479
NDST1 81479,81479
NLGN4X 81405,81404
OPHN1 81479,81479
PAK3 81479,81479
PIDD1 81479,81479
PQBP1 81405,81404
PRSS12 81479,81479
PTCHD1 81479,81479
RAB39B 81479,81479
RPS6KA3 81479,81479
SCN2A 81479,81479
SCN8A 81479,81479
SDK2 81479,81479
SETBP1 81479,81479
SETD5 81479,81479
SHANK3 81479,81479
SIN3A 81479,81479
SLAIN1 81479,81479
SLC16A2 81405,81404
SLC2A1 81405,81479
SLC6A8 81479,81479
SLC9A6 81406,81479
SMC1A 81479,81479
SNX14 81479,81479
SPATA13 81479,81479
STXBP1 81406,81479
SUMF2 81479,81479
SYNRG 81479,81479
TBC1D23 81479,81479
TBC1D24 81479,81479
TBR1 81479,81479
TCF4 81406,81405
TET1 81479,81479
TRAPPC6B 81479,81479
TRAPPC9 81479,81479
TRIO 81479,81479
TSPAN7 81479,81479
TUSC3 81479,81479
UBA7 81479,81479
UBE2A 81479,81479
UPF3B 81479,81479
USP44 81479,81479
VPS35 81479,81479
WASHC4 81479,81479
ZBTB11 81479,81479
ZC3H14 81479,81479
ZDHHC9 81479,81479
ZNF711 81479,81479
Full Panel Price* $1280
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
5059 Genes x (110) $1280 81302, 81304, 81403, 81404(x5), 81405(x6), 81406(x5), 81407, 81479(x200) Add to Order
Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

Targeted Testing

For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 26 days.

Clinical Sensitivity

To date no comprehensive studies have been conducted to determine the combined contribution of the genes included in this sequencing panel. Consequently, the overall clinical sensitivity of this test cannot be estimated. Because this panel provides at least 99.6% coverage of all coding exons of the genes listed, and because the great majority of pathogenic variants reported to date are detectable by sequencing, the analytical sensitivity should be high .

Genetic causes of intellectual disability (ID) have been detected in 25–50% of the cases and pathogenic CNVs have a diagnostic yield of ~10-15% (McLaren and Bryson 1987; Kaufman et al. 2010. PubMed ID: 21124998). However, CMA analysis is limited in its ability to identify low-level mosaicism and balanced translocations (Miller et al. 2010. PubMed ID: 20466091) and up to ~3% of pathogenic variants are estimated to be located within non-coding regions of the genome (Vissers et al. 2016. PubMed ID: 26503795; Chiurazzi and Pirozzi. 2016. PubMed ID: 27127621). Notably, the etiology of the majority (up to ~60%) of ID cases remains unknown; however with exome sequencing this percentage is rapidly altering (Kaufman et al. 2010. PubMed ID: 21124998; Topper et al. 2011. PubMed ID: 21627642). Nevertheless, trio-based studies are reported to increase the molecular diagnostic rate to ~30%-40% for developmental phenotypes (Wright et al. 2015. PubMed ID: 25529582).

A total of 69 out of the 110 genes in this sequencing panel have been reported to have pathogenic large deletions and/or duplications leading to intellectual disability (Human Gene Mutation Database).

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Clinical Features

Intellectual Disability (ID) (also referred to as mental retardation), is a heterogeneous group of neurodevelopmental disorders. ID is characterized by significant impairment of cognitive and adaptive development (with intelligence quotient, IQ<70) due to abnormalities of brain structure and/or function (American Association of Intellectual and Developmental Disabilities, AAIDD). ID is not a single entity, but rather a general symptom of neurologic dysfunction diagnosed before 18 years of age in 1–3% of the population, irrespective of any social class and culture (Vissers et al. 2016. PubMed ID: 26503795; Kaufman et al. 2010. PubMed ID: 21124998).

Traditionally, non-syndromic ID (NS-ID) is defined by the presence of intellectual disability as the sole clinical feature. However, it is often challenging to rule out the presence of more subtle neurological anomalies and psychiatric disorders in these patients, as they may be less apparent or difficult to diagnose due to cognitive impairment. Additionally, symptoms of some syndromic ID (S-ID) may be very subtle, making the distinction between Syndromic ID and NS-ID difficult (Kaufman et al. 2010. PubMed ID: 21124998; Mehregan et al. 2016. PubMed ID: 27179170). Interestingly, X-linked Intellectual Disability (XLID) contributes almost 10-15% of ID cases in males, and non-syndromic XLID is more prevalent as it accounts for almost two third of the XLID cases (de Brouwer et al. 2007. PubMed ID: 17221867).

ID can be caused by environmental and/or genetic factors and the higher prevalence of mild ID in areas of lower socioeconomic status and developing countries has been suggested to be due to environmental factors (Kaufman et al. 2010. PubMed ID: 21124998; Emerson and Brigham. 2015. PubMed ID: 24797435). The clinical heterogeneity of ID is reflected with extreme genetic heterogeneity, and a genetic diagnosis is still lacking in most cases (Mefford et al. 2012. PubMed ID: 22356326).

Genetics

Although non-genetic factors (infection, trauma) can result in cognitive impairment, most severe forms of intellectual disability (ID) have a genetic basis, with underlying pathogenic variants occurring at scales of resolution ranging from large cytogenetic abnormalities to single nucleotide variants and even epigenetic alterations (Topper et al. 2011. PubMed ID: 21627642). A large number of studies have pointed out the association of chromosomal abnormalities (Trisomy 21, Fragile X syndrome, translocations, recurrent microdeletions/duplications of autosomes, etc.) and pathogenic copy number variations (CNV) with ID cases, and this will likely contribute to the discovery of many future ID genes (Ropers and Hamel. 2005. PubMed ID: 15630421; Rauch et al. 2006. PubMed ID: 16917849, Zahir and Friedman. 2007. PubMed ID: 17850622). Chromosomal abnormalities and CNVs can explain ~15% and ~10% of ID cases, respectively. The fragile X mental retardation 1 (FMR1) gene remains the most commonly mutated gene in ID (~0.5% of ID cases).

Genetic causes of ID have been detected in roughly 25–50% of the cases, and this percentage increases proportionally with the severity (Kaufman et al. 2010. PubMed ID: 21124998). Since NS-ID presents with intellectual impairment as the sole feature, genes that are involved are likely related to the processes of learning and memory. Understanding the genetics of a complex disorder like NS-ID is also relevant to genetic counseling in families with affected individuals, particularly where consanguinity is involved (Modell and Darr. 2002. PubMed ID: 11972160).

This test involves sequencing of genes that have previously been reported to be defective in NS-ID cases with varied inheritance patterns, such as X-linked (at least 38 genes), autosomal recessive (at least 42 genes), autosomal dominant/de novo (at least 28 genes), and mixed i.e. both autosomal dominant and recessive (at least 2 genes) (Harripaul et al. 2017. PubMed ID: 28397838). Notably, pathogenic variations within at least 70 genes of this panel have also been implicated in patients with syndromic ID (S-ID).

Testing Strategy

For this Next Generation Sequencing (NGS) test, sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization kit, followed by massively parallel sequencing of the captured DNA fragments.

For Sanger sequencing, polymerase chain reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All CNVs are confirmed using another technology such as aCGH, MLPA, or PCR before they are reported.

This panel provides at least 99.6% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as >20X NGS reads or Sanger sequencing.

Genes without complete coverage: AP1S2, AFF2, AFF3, ARID1B, ARHGEF9, BRWD3, CDH15, CHD2, CIC, DEAF1, DMBT1, ELP2, FGD1, FMN2, HUWE1, IL1RAPL1, IQSEC2, MAGEA11, MECP2, MED13L, MED25, MEF2C, MPDZ, NAA10, NLGN4X, PAK3, RPS6KA3, SCN2A, SDK2, SETBP1, SETD5, SHANK3, SIN3A. SLC16A2, SLC6A8, SUMF2, TBC1D24, TET1, TRIO, UPF3B and VPS35. A full list of regions not covered by NGS or Sanger sequencing is available upon request.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

This test is primarily implicated for the patients with non-syndromic intellectual disability (NS-ID) i.e. individuals with mild to severe intellectual disabilities having no apparent co-morbid features. But considering that pathogenic variants of at least 70 genes of this panel can also develop S-ID, the presence of some subtle symptoms (additional to ID) in these patients cannot be ruled out.

Genes

Official Gene Symbol OMIM ID
ABI2 606442
ACSL4 300157
ADGRG2 300572
ADNP 611386
AFF2 300806
AFF3 601464
AP1S2 300629
ARHGEF9 300429
ARID1B 614556
ARX 300382
ATRX 300032
BCL11A 606557
BDNF 113505
BRWD3 300553
CAPS 114212
CC2D1A 610055
CDH15 114019
CHD2 602119
CIC 612082
CLCN4 302910
CNTNAP2 604569
CRBN 609262
CTNNB1 116806
CUL4B 300304
DCPS 610534
DDX3X 300160
DEAF1 602635
DLG3 300189
DMBT1 601969
ELP2 616054
EXTL3 605744
FBXO47 609498
FGD1 300546
FMN2 606373
FOXG1 164874
FTSJ1 300499
GATAD2B 614998
GDI1 300104
GRIA3 305915
GRIN1 138249
GRIN2B 138252
HIVEP2 143054
HUWE1 300697
IL1RAPL1 300206
IQSEC2 300522
KDM5C 314690
KIRREL3 607761
LAMC1 150290
MAGEA11 300344
MAN1B1 604346
MAP3K7 602614
MAPK8 601158
MBD5 611472
MECP2 300005
MED13L 608771
MED23 605042
MED25 610197
MEF2C 600662
METTL23 615262
MPDZ 603785
MYT1L 613084
NAA10 300013
NDST1 600853
NLGN4X 300427
OPHN1 300127
PAK3 300142
PIDD1 605247
PQBP1 300463
PRSS12 606709
PTCHD1 300828
RAB39B 300774
RPS6KA3 300075
SCN2A 182390
SCN8A 600702
SDK2 607217
SETBP1 611060
SETD5 615743
SHANK3 606230
SIN3A 607776
SLAIN1 610491
SLC16A2 300095
SLC2A1 138140
SLC6A8 300036
SLC9A6 300231
SMC1A 300040
SNX14 616105
SPATA13 613324
STXBP1 602926
SUMF2 607940
SYNRG 607291
TBC1D23 617687
TBC1D24 613577
TBR1 604616
TCF4 602272
TET1 607790
TRAPPC6B 610397
TRAPPC9 611966
TRIO 601893
TSPAN7 300096
TUSC3 601385
UBA7 191325
UBE2A 312180
UPF3B 300298
USP44 610993
VPS35 601501
WASHC4 615748
ZBTB11 0
ZC3H14 613279
ZDHHC9 300646
ZNF711 314990
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Aarskog Syndrome XL 305400
Al-Raqad Syndrome AR 616459
Allan-Herndon-Dudley Syndrome XL 300523
ATR-X Syndrome XL 301040
Autism, Susceptibility To, X-Linked 2 XL 300495
Autism, Susceptibility to, X-linked 4 XL 300830
Basel-Vanagait-Smirin-Yosef Syndrome AR 616449
Cerebral Creatine Deficiency Syndrome 1 XL 300352
Coffin-Siris Syndrome 1 AD 135900
Cornelia de Lange syndrome 2 XL 300590
Cortical Dysplasia-Focal Epilepsy Syndrome AR 610042
Dias-Logan Syndrome AD 617101
Dyskinesia, Seizures, and Intellectual Developmental Disorder AR 617171
Epileptic encephalopathy, childhood-onset AD 615369
Epileptic Encephalopathy, Early Infantile, 11 AD 613721
Epileptic Encephalopathy, Early Infantile, 13 AD 614558
Epileptic Encephalopathy, Early Infantile, 16 AD, AR 615338
Epileptic Encephalopathy, Early Infantile, 4 AD 612164
Epileptic Encephalopathy, Early Infantile, 8 XL 300607
Frontometaphyseal Dysplasia 2 AD 617137
Glut1 Deficiency Syndrome 1 AD, AR 606777
Helsmoortel-van der Aa Syndrome AD 615873
Hydrocephalus, Nonsyndromic, Autosomal Recessive 2 AR 615219
Immunoskeletal Dysplasia with Neurodevelopmental Abnormalities AR 617425
Mental Retardation and Distinctive Facial Features with or without Cardiac Defects AD 616789
Mental Retardation, Autosomal Dominant 1 AD 156200
Mental Retardation, Autosomal Dominant 18 AD 615074
Mental Retardation, Autosomal dominant 19 AD 615075
Mental Retardation, Autosomal Dominant 23 AD 615761
Mental Retardation, Autosomal Dominant 29 AD 616078
Mental Retardation, Autosomal Dominant 3 AD 612580
Mental Retardation, Autosomal Dominant 39 AD 616521
Mental Retardation, Autosomal Dominant 4 AD 612581
Mental Retardation, Autosomal Dominant 43 AD 616977
Mental Retardation, Autosomal Dominant 44 AD 617061
Mental Retardation, Autosomal Dominant 6 AD 613970
Mental Retardation, Autosomal Dominant 8 AD 614254
Mental Retardation, Autosomal Recessive 1 AR 249500
Mental Retardation, Autosomal Recessive 13 AR 613192
Mental Retardation, Autosomal Recessive 15 AR 614202
Mental Retardation, Autosomal Recessive 18 AR 614249
Mental Retardation, Autosomal Recessive 2 AR 607417
Mental Retardation, Autosomal Recessive 3 AR 608443
Mental Retardation, Autosomal Recessive 43 AR 615817
Mental Retardation, Autosomal Recessive 44 AR 615942
Mental Retardation, Autosomal Recessive 46 AR 616116
Mental Retardation, Autosomal Recessive 47 AR 616193
Mental Retardation, Autosomal Recessive 56 AR 617125
Mental Retardation, Autosomal Recessive 58 AR 617270
Mental Retardation, Autosomal Recessive 7 AR 611093
Mental Retardation, Stereotypic Movements, Epilepsy, And/Or Cerebral Malformations AD 613443
Mental Retardation, X-Linked 1/78 XL 309530
Mental Retardation, X-Linked 102 XL 300958
Mental Retardation, X-Linked 19 AD 300844
Mental Retardation, X-Linked 21 XL 300143
Mental Retardation, X-Linked 30 XL 300558
Mental Retardation, X-Linked 41 XL 300849
Mental Retardation, X-linked 49 XL 300114
Mental Retardation, X-Linked 58 XL 300210
Mental Retardation, X-Linked 63 XL 300387
Mental Retardation, X-Linked 72 XL 300271
Mental Retardation, X-Linked 9 XL 309549
Mental Retardation, X-Linked 90 XL 300850
Mental Retardation, X-Linked 93 XL 300659
Mental Retardation, X-Linked 97 XL 300803
Mental Retardation, X-linked, FRAXE Type XL 309548
Mental Retardation, X-Linked, Syndromic 13 XL 300055
Mental Retardation, X-Linked, Syndromic 14 XL 300676
Mental Retardation, X-Linked, Syndromic, Christianson Type XL 300243
Mental Retardation, X-Linked, Syndromic, Claes-Jensen Type XL 300534
Mental Retardation, X-Linked, Syndromic, Nascimento Type XL 300860
Mental Retardation, X-Linked, Syndromic, Raymond Type XL 300799
Mental Retardation, X-Linked, Syndromic, Turner Type XL 300706
Mental Retardation, X-Linked, Syndromic, Wu Type XL 300699
Mental Retardation, X-Linked, With Or Without Seizures, Arx-Related XL 300419
Mental Retardation, X-Linked, With Short Stature, Hypogonadism, And Abnormal Gait XL 300354
Neurodevelopmental Disorder with Microcephaly, Epilepsy, and Brain Atrophy AD 617862
Obsessive-Compulsive Disorder AD 164230
Ogden Syndrome XL 300855
Parkinson Disease 17 AD 614203
Pettigrew Syndrome XL 304340
Phelan-Mcdermid Syndrome AD 606232
Pitt-Hopkins Syndrome AD 610954
Pontocerebellar Hypoplasia Type 11 AR 617695
Renpenning Syndrome 1 XL 309500
Rett Syndrome, Congenital Variant AD 613454
Spinocerebellar Ataxia, Autosomal Recessive 20 AR 616354
Vas Deferens, Congenital Bilateral Aplasia of, X-linked XL 300985
Witteveen-Kolk Syndrome AD 613406
X-LinkedMental Retardation With Cerebellar Hypoplasia And Distinctive Facial Appearance XL 300486

Related Test

Name
PGxome®

CONTACTS

Genetic Counselors
Geneticist
Citations
  • de Brouwer et al. 2007. PubMed ID: 17221867
  • Emerson and Brigham. 2015. PubMed ID: 24797435
  • Harripaul et al. 2017. PubMed ID: 28397838
  • Human Gene Mutation Database (Bio-base).
  • Kaufman et al. 2010. PubMed ID: 21124998
  • McLaren and Bryson. 1987. PubMed ID: 3322329
  • Mefford et al. 2012. PubMed ID: 22356326
  • Mehregan et al. 2016. PubMed ID: 27179170
  • Miller et al. 2010. PubMed ID: 20466091
  • Modell and Darr. 2002. PubMed ID: 11972160
  • Rauch et al. 2006. PubMed ID: 16917849
  • Ropers and Hamel. 2005. PubMed ID: 15630421
  • Topper et al. 2011. PubMed ID: 21627642
  • Vissers et al. 2016. PubMed ID: 26503795
  • Wright et al. 2015. PubMed ID: 25529582
  • Zahir and Friedman. 2007. PubMed ID: 17850622
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TEST METHODS

Exome Sequencing with CNV Detection

Test Procedure

For PGxome® we use Next Generation Sequencing (NGS) technologies to cover the coding regions of targeted genes plus 10 bases of flanking non-coding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. As required, genomic DNA is extracted from patient specimens. Patient DNA corresponding to these regions is captured using Agilent Clinical Research Exome hybridization probes. Captured DNA is sequenced on the NovaSeq 6000 using 2x150 bp paired-end reads (Illumina, San Diego, CA, USA). The following quality control metrics are generally achieved: >97% of target bases are covered at >20x, and mean coverage of target bases >120x. Data analysis and interpretation is performed by the internally developed software Titanium-Exome. In brief, the output data from the NovaSeq 6000 is converted to fastqs by Illumina Bcl2Fastq, and mapped by BWA. Variant calls are made by the GATK Haplotype caller and annotated using in house software and SnpEff. Variants are filtered and annotated using VarSeq (www.goldenhelix.com).

For Sanger sequencing, polymerase chain reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All CNVs are confirmed using another technology such as aCGH, MLPA, or PCR before they are reported.

Analytical Validity

NextGen Sequencing: As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.

In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable.

Copy Number Variant Analysis: The PGxome test detects most larger deletions and duplications including intragenic CNVs and large cytogenetic events; however aberrations in a small percentage of regions may not be accurately detected due to sequence paralogy (e.g., pseudogenes, segmental duplications), sequence properties, deletion/duplication size (e.g., 1-3 exons vs. 4 or more exons), and inadequate coverage. In general, sensitivity for single, double, or triple exon CNVs is ~70% and for CNVs of four exon size or larger is >95%, but may vary from gene-to-gene based on exon size, depth of coverage, and characteristics of the region.

Analytical Limitations

Interpretation of the test results is limited by the information that is currently available. Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

When sequencing does not reveal any heterozygous differences from the reference sequence, we cannot be certain that we were able to detect both patient alleles.

For technical reasons, the PGxome test is not 100% sensitive. Some exons cannot be efficiently captured, and some genes cannot be accurately sequenced because of the presence of multiple copies in the genome. Therefore, a small fraction of sequence variants will not be detected.

We sequence coding exons for all available transcripts plus 10 bp of flanking non-coding DNA for each exon. We also sequence other regions within or near genes in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere.  Unless specifically indicated, test reports contain no information about other portions of genes.

In most cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants due to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient's nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during amplification.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes if taken from whole blood). Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

Balanced translocations or inversions are only rarely detected.

Certain types of sex chromosome aneuploidy may not be detected.  

Our ability to detect CNVs due to somatic mosaicism is limited.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics. However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.

A negative finding does not rule out a genetic diagnosis.

Genetic counseling to help to explain test results to the patients and to discuss reproductive options is recommended.

Order Kits

Ordering Options


myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
REQUISITION FORM
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

SPECIMEN TYPES
WHOLE BLOOD

(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.

DNA

(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.

CELL CULTURE

(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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