X-Linked Intellectual Disability Sequencing Panel with CNV Detection

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits


Test Code Test Copy GenesCPT Code Copy CPT Codes
2675 ABCD1 81405, 81479 Add to Order
ACSL4 81479, 81479
AFF2 81479, 81479
AIFM1 81479, 81479
ALG13 81479, 81479
AP1S2 81479, 81479
ARHGEF9 81479, 81479
ARX 81404, 81403
ATP6AP2 81479, 81479
ATP7A 81479, 81479
ATRX 81479, 81479
BCOR 81479, 81479
BRWD3 81479, 81479
CASK 81479, 81479
CCDC22 81479, 81479
CDKL5 81406, 81405
CLCN4 81479, 81479
CLIC2 81479, 81479
CNKSR2 81479, 81479
CUL4B 81479, 81479
DCX 81405, 81479
DKC1 81479, 81479
DLG3 81479, 81479
FGD1 81479, 81479
FMR1 81479, 81479
FTSJ1 81406, 81405
GDI1 81479, 81479
GPC3 81479, 81479
GRIA3 81479, 81479
HCFC1 81479, 81479
HDAC8 81479, 81479
HPRT1 81479, 81479
HSD17B10 81479, 81479
HUWE1 81479, 81479
IDS 81405, 81479
IL1RAPL1 81479, 81479
IQSEC2 81479, 81479
KDM5C 81479, 81408
L1CAM 81407, 81479
LAMP2 81405, 81479
MAOA 81479, 81479
MBTPS2 81479, 81479
MECP2 81302, 81304
MED12 81479, 81479
MID1 81479, 81479
NAA10 81479, 81479
NDP 81404, 81479
NEXMIF 81479, 81479
NHS 81479, 81479
NLGN4X 81405, 81404
NSDHL 81479, 81479
OCRL 81479, 81479
OFD1 81479, 81479
OPHN1 81479, 81479
OTC 81405, 81479
PAK3 81479, 81479
PCDH19 81405, 81479
PDHA1 81406, 81405
PGK1 81479, 81479
PHF6 81479, 81479
PHF8 81479, 81479
PLP1 81405, 81404
PQBP1 81405, 81404
PRPS1 81479, 81479
PTCHD1 81479, 81479
RAB39B 81479, 81479
RBM10 81479, 81479
RPL10 81479, 81479
RPS6KA3 81479, 81479
SLC16A2 81405, 81404
SLC9A6 81406, 81479
SMC1A 81479, 81479
SMS 81479, 81479
SYN1 81479, 81479
SYP 81479, 81479
UBE2A 81479, 81479
UPF3B 81479, 81479
USP9X 81479, 81479
WDR45 81479, 81479
ZC4H2 81479, 81479
ZDHHC9 81479, 81479
Full Panel Price* $2940.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
2675 Genes x (81) $2940.00 81302, 81304, 81403, 81404(x6), 81405(x13), 81406(x4), 81407, 81408, 81479(x134) Add to Order
Pricing Comment

CPT codes 81470 and 81471 can be used if at least 60 of the genes in the panel are analyzed. If you would like to order a subset of these genes contact us to discuss pricing.

Targeted Testing

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

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Extrapolating from previously published studies of next generation sequencing in large cohorts of patients with XLID, we predict that our XLID Panel will identify pathogenic variants in 20-40% of Fragile X negative XLID cases (de Brouwer et al 2007; Hu et al 2015). Specific clinically recognizable features accompanying the XLID can increase the success rate of mutation detection.

Approximately 5-10% of cases of intellectual disability in males are due to copy number variations (CNV) on the X chromosome (Madrigal et al. 2007). A total of 64 out of the 81 genes in this XLID panel have been reported to have pathogenic large deletions and/or duplications causative for X-linked intellectual disability (Human Gene Mutation Database). Genes in which large deletions and duplications are not rare include ABCD1, ARX, ATP7A, ATRX, CASK, GPC3, IDS, IL1RAPL1, MECP2, OTC, PCDH19, PTCHD1, RPS6KA3, and SLC16A2.

If the result of this panel is negative, we can reflex to our exome test, PGxome.

See More

See Less

Clinical Features

Intellectual Disability is a group of genetically heterogeneous disorders characterized by substantial impairment in cognitive abilities, communication, self-direction, and social and behavioral adaptive skills. The assessment of intelligence is across three domains which are conceptual, social, and practical ability (Diagnostic and Statistical Manual of Mental Disorder (DSM-5)). Intellectual disability is defined by an intelligence quotient (IQ) below 70 diagnosed before the age of 18. Approximately 1–3% of the population suffers intellectual disability. Genetic etiologies are found in approximately two-thirds of cases (Raymond et al 2006; Basel-Vanagaite 2008). X-linked Intellectual Disability (XLID) contributes 10%-15% of cases of Intellectual disability in males. In the general population, the ratio of individuals with intellectual disability between males and females is 1.25:1 which is probably due to a role of defects on the X chromosome (Raymond et al 2006). XLID can be divided into syndromic forms, which are characterized by XLID accompanied by malformations, dysmorphic features, or neurological abnormalities, and non-syndromic forms, which are characterized by XLID without any additional features. Non-syndromic XLID is more common and it accounts for two third of XLID patients (de Brouwer et al 2007). Syndromic X-linked Intellectual Disability: In this panel, there are 44 established syndromic XLID genes. For example, SLC16A2 for Allan-Herndon-Dudley syndrome, RPS6KA3 for Coffin Lowry syndrome, MECP2 for Rett syndrome, HPRT1 for Lesch-Nyhan syndrome, and OCRL for Lowe syndrome (for details, see the table below). Non-syndromic X-linked Intellectual Disability: In this panel, there are 38 established non-syndromic XLID genes (for details, see the table below).


XLID is a heterogeneous disorder can be inherited either in X-linked recessive (XLR), or X-linked dominant (XLD) manner with syndromic or non-syndromic phenotypes. There are no major mutational hot spots for XLID genes, except for CGG repeat expansions in FMR1 which is considered to be the most common single gene defect in XLID (Basel-Vanagaite, 2008). The identified XLID proteins belong to different pathways and networks with established roles in cognitive function and intellectual disability (Hu et al 2015; de Brouwer et al 2007). This panel focuses on genes which are specifically selected for an established monogenic form of XLID, after comparing results from different large scale cohorts (Renieri et al 2005; De Brouwer et al 2007; Tarpey et al 2009; Piton et al 2013; Hu et al 2015). A wide variety of causative variants (missense, nonsense, splicing, small deletions and insertions) have been reported. Except for a few genes, most genes in this panel have also been reported to have large deletions/duplications and complex genomic rearrangements (Mignon-Ravix et al. 2014; Human Gene Mutation Database). See individual gene test descriptions for more information on molecular biology of gene products. The following Table indicates disorders and its mode of inheritance by genes (XL: X-linked, XLD: X-linked dominant inheritance, XLR: X-linked recessive inheritance)

Genes Disorders and Mode of Inheritance
ACSL4 Mental retardation, X-linked 63, XL
ABCD1 Adrenoleukodystrophy, XLR
AFF2 Mental retardation, X-linked, fragile site, folic acid sensitive type, XLR
AIFM1 Cowchock syndrome, XLR
ALG13 Congenital disorder of glycosylation, type Is, XLD
AP1S2 Mental retardation, X-linked syndromic 5, XLR
ARHGEF9 Intellectual disability associated with epileptic encephalopathy, early infantile, XL
ARX Mental retardation, X-linked syndromic and non-syndromic, XL
ATP6AP2 Mental retardation, X-linked, XLR
ATP7A Menkes disease, XLR
ATRX Alpha-thalassemia/mental retardation syndrome, XLR
BCOR Oculofaciocardiodental syndrome, XLD
BRWD3 Mental retardation, X-linked 93, XLR
CASK FG sndrome 4, XLR
CCDC22 Ritscher-Schinzel syndrome 2, XLR
CDKL5 Epileptic encephalopathy, early infantile, 2, XLD
CLCN4 Intellectual disability, XL
CLIC2 Intellectual disability, XL
CNKSR2 X-linked intellectual disability and seizures, non-syndromic, XL
CUL4B Mental retardation, X-linked, syndromic 15 (Cabezas type), XLR
DCX Lissencephaly, X-linked, XL
DKC1 Dyskeratosis congenita, X-linked, XLR
DLG3 Mental retardation, X-linked 90, XLR
FGD1 Aarskog-Scott syndrome, XLR
FMR1 Fragile X syndrome, XLR
FTSJ1 Mental retardation, X-linked 9, XL
GDI1 Mental retardation, X-linked 41, XL
GPC3 Simpson-Golabi-Behmel syndrome, type 1, XLR
GRIA3 Mental retardation, X-linked 94, XLR
HCFC1 Mental retardation, X-linked 3 (methylmalonic acidemia and homocysteinemia, cblX type ), XLR
HDAC8 Cornelia de Lange syndrome 5, XLR
HPRT1 Lesch-Nyhan syndrome, XLR
HSD17B10 Mental retardation, X-linked, XLR
HUWE1 Mental retardation, X-linked, non-syndromic, XL
IDS Mucopolysaccharidosis II, XLR
IL1RAPL1 Mental retardation, X-linked 21/34, XLR
IQSEC2 Mental retardation, X-linked 1, syndromic or non-syndromic, XL
KDM5C Mental retardation, X-linked, syndromic, Claes-Jensen type, XLR
L1CAM MASA syndrome, XLR
LAMP2 Danon disease, XLD
MAOA Brunner syndrome, XLR
MBTPS2 IFAP syndrome with or without BRESHECK syndrome, XLR
MECP2 Rett syndrome, XLD
MED12 Lujan-Fryns syndrome, Opitz-Kaveggia syndrome, XLR
MID1 Opitz G/BBB syndrome, type I, XLR
NAA10 Interlectual disability with long QT, XL
NDP Norrie disease, XLR
NEXMIF/KIAA2022 Mental retardation, X-linked 98, XLR
NHS Nance-Horan syndrome, XLD
NLGN4X Mental retardation, X-linked, XL
NSDHL CK syesndrome, XLR
OCRL Lowe syndrome, XLR
OFD1 Simpson-Golabi-Behmel syndrome, type 2, XLR
OPHN1 Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, XLR
OTC Ornithine transcarbamylase deficiency, XLR
PAK3 Mental retardation, X-linked 30/47, XLR
PCDH19 Epileptic encephalopathy, early infantile, 9 XL
PDHA1 Pyruvate dehydrogenase E1-alpha deficiency, XLD
PGK1 Phosphoglycerate kinase 1 deficiency, XLR
PHF6 Borjeson-Forssman-Lehmann syndrome, XLR
PHF8 Mental retardation syndrome, X-linked, Siderius type, XL
PLP1 Pelizaeus-Merzbacher disease, XLR
PQBP1 Renpenning syndrome, XLR
PRPS1 Arts syndrome, XLR
PTCHD1 Intellectual disability, Autism, susceptibility to, X-linked 4, XLR
RAB39B Mental retardation, X-linked 72, Waisman syndrome, early onset Parkinson disease, XLR
RBM10 Intellectual disability, XL
RPL10 Intellectual disability XL
RPS6KA3 Coffin-Lowry syndrome, XLD
SLC16A2 Allan-Herndon-Dudley syndrome, XLR
SLC9A6 Mental retardation, X-linked syndromic, Christianson type, XLD
SMC1A Intellectual disabililty, XL
SMS Mental retardation, X-linked, Snyder-Robinson type, XLR
SYN1 Epilepsy, X-linked, with variable learning disabilities and behavior disorders, XL
SYP Mental retardation, X-linked 96, XLD
UBE2A Mental retardation, X-linked syndromic, Nascimento-type, XLR
UPF3B Mental retardation, X-linked, syndromic 14, XLR
USP9X Mental retardation, X-linked 99, XLR
WDR45 Neurodegeneration with brain iron accululation 5, XLD
ZC4H2 Wieacker-Wolff syndrome, XLR
ZDHHC9 Mental retardation, X-linked syndromic, Raymond type, XL

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. Additional Sanger sequencing is performed for regions not captured or with insufficient number of sequence reads. All reported pathogenic, likely pathogenic, and variants of uncertain significance are confirmed by Sanger sequencing.

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 full coverage of all coding exons of the genes listed, plus ~10 bases of flanking noncoding DNA. We define coverage as ≥20X NGS reads or Sanger sequencing.

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 X-lined Intellectual Disability NGS Panel is recommended for patients with syndromic or non-syndromic intellectual disability inherited in either X- linked dominant or X-linked recessive manner who are negative for the fragile X repeat expansion. Prenatal diagnosis is possible, if the genetic diagnosis has been firmly established in an affected family member.


Name Inheritance OMIM ID
Aarskog Syndrome XL 305400
Adrenoleukodystrophy XL 300100
Allan-Herndon-Dudley Syndrome XL 300523
Arts Syndrome XL 301835
ATR-X Syndrome XL 301040
Autism, Susceptibility To, X-Linked 2 XL 300495
Autism, Susceptibility to, X-linked 4 XL 300830
Autism, Susceptibility To, X-Linked 5 XL 300847
Borjeson-Forssman-Lehmann Syndrome XL 301900
CK syndrome XL 300831
Coffin-Lowry Syndrome XL 303600
Cornelia de Lange syndrome 2 XL 300590
Cornelia de Lange syndrome 5 XL 300882
Cowchock Syndrome XL 310490
Danon Disease XL 300257
Dyskeratosis Congenita X-Linked XL 305000
Epilepsy, X-Linked, With Variable Learning Disabilities And Behavior Disorders XL 300491
Epileptic Encephalopathy, Early Infantile, 2 XL 300672
Epileptic Encephalopathy, Early Infantile, 36 XL 300884
Epileptic Encephalopathy, Early Infantile, 8 XL 300607
Epileptic Encephalopathy, Early Infantile, 9 XL 300088
Fragile X Syndrome XL 300624
Ichthyosis Follicularis Atrichia Photophobia Syndrome XL 308205
Lesch-Lyhan Syndrome XL 300322
Lowe Syndrome XL 309000
Lujan-Fryns Syndrome XL 309520
Menkes Kinky-Hair Syndrome XL 309400
Mental Retardation, with or without Nystagmus XL 300422
Mental Retardation, X-Linked 1/78 XL 309530
Mental Retardation, X-Linked 21 XL 300143
Mental Retardation, X-Linked 3 (Methylmalonic Acidemia and Homocysteinemia, cblX Type) XL 309541
Mental Retardation, X-Linked 30 XL 300558
Mental Retardation, X-Linked 41 XL 300849
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 96 XL 300802
Mental Retardation, X-linked 98 XL 300912
Mental Retardation, X-linked 99 XL 300919
Mental retardation, X-linked 99, Syndromic, Female-Restricted XL 300968
Mental Retardation, X-linked, FRAXE Type XL 309548
Mental Retardation, X-Linked, Syndromic 10 XL 300220
Mental Retardation, X-Linked, Syndromic 14 XL 300676
Mental Retardation, X-linked, Syndromic 32 XL 300886
Mental Retardation, X-Linked, Syndromic, Christianson Type XL 300243
Mental Retardation, X-Linked, Syndromic, Claes-Jensen Type XL 300534
Mental Retardation, X-Linked, Syndromic, Hedera Type XL 300423
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 Short Stature, Hypogonadism, And Abnormal Gait XL 300354
Monoamine Oxidase A Deficiency XL 300615
Mucopolysaccharidosis, MPS-II XL 309900
Nance-Horan Syndrome XL 302350
Neurodegeneration With Brain Iron Accumulation 5 XL 300894
Norrie Disease XL 310600
Oculofaciocardiodental Syndrome XL 300166
Ogden Syndrome XL 300855
Opitz G/BBB Syndrome, Type I XL 300000
Ornithine Carbamoyltransferase Deficiency XL 311250
Pelizaeus-Merzbacher Disease XL 312080
Pettigrew Syndrome XL 304340
Phosphoglycerate Kinase 1 Deficiency XL 300653
Pyruvate Dehydrogenase E1-Alpha Deficiency XL 312170
Renpenning Syndrome 1 XL 309500
Rett Syndrome XL 312750
Ritscher-Schinzel Syndrome 2 XL 300963
Siderius X-Linked Mental Retardation Syndrome XL 300263
Simpson-Golabi-Behmel Syndrome XL 312870
Simpson-Golabi-Behmel Syndrome, Type 2 XL 300209
Snyder Robinson Syndrome XL 309583
Spastic Paraplegia 1 XL 303350
TARP Syndrome XL 311900
Wieacker-Wolff Syndrome XL 314580
X-Linked Lissencephaly XL 300067
X-Linked Lissencephaly 2 XL 300215
X-LinkedMental Retardation With Cerebellar Hypoplasia And Distinctive Facial Appearance XL 300486

Related Tests

AIFM1-Related Disorders via the AIFM1 Gene
HCFC1-Related Disorders via the HCFC1 Gene
NSDHL-Related Disorders via the NSDHL Gene
OFD1-Related Disorders via the OFD1 Gene
PLP1-Related Disorders via the PLP1 Gene
PRPS1-Related Disorders
Aarskog-Scott Syndrome via the FGD1 Gene
Allan-Herndon-Dudley Syndrome or Monocarboxylate Transporter 8 Deficiency via the SLC16A2 Gene
Alpha-Thalassemia X-linked Intellectual Disability Syndrome via the ATRX Gene
Anophthalmia / Microphthalmia Sequencing Panel
Autism Spectrum Disorders (ASD) via the NLGN4X Gene
Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Sequencing Panel with CNV Detection
Beta-propeller Protein-associated Neurodegeneration (BPAN) via the WDR45 Gene
Cabezas X-Linked Mental Retardation Syndrome via the CUL4B Gene
CASK Related Disorders, Microcephaly with Pontine and Cerebellar Hypoplasia, X-linked intellectual disability with or without Nystagmus and FG Syndrome Type 4 via the CASK Gene
Charcot Marie Tooth - Axonal Neuropathy Sequencing Panel
Charcot Marie Tooth - Comprehensive Sequencing Panel
Christianson Type X-Linked Mental Retardation via the SLC9A6 Gene
Ciliopathy Sequencing Panel
Classic Lissencephaly via the DCX Gene
Complex Hereditary Spastic Paraplegia Sequencing Panel with CNV Detection
Comprehensive Cardiology Sequencing Panel with CNV Detection
Comprehensive Inherited Retinal Dystrophies (includes RPGR ORF15) Sequencing Panel with CNV Detection
Comprehensive Neuropathy Sequencing Panel
Congenital Cataracts Sequencing Panel
Congenital Hypothyroidism and Thyroid Hormone Resistance Sequencing Panel
Cornelia de Lange Syndrome and Cornelia de Lange Syndrome-Related Disorders Sequencing Panel
Cornelia de Lange Syndrome Sequencing Panel
Cornelia de Lange Syndrome via the HDAC8 Gene
Cornelia de Lange Syndrome via the SMC1A Gene
Danon Disease/Glycogen Storage Disease IIb via the LAMP2 Gene
Dent Disease Sequencing Panel
Dilated Cardiomyopathy Sequencing Panel with CNV Detection
Disorders of Fatty Acid Oxidation Sequencing Panel
Disorders of Sex Development and Infertility Sequencing Panel with CNV Detection
Disorders of Sex Development Sequencing Panel with CNV Detection
Disorders Related to Metabolism of Cobalamin, Folate and Homocysteine Sequencing Panel
Distal Hereditary Motor Neuropathy Sequencing Panel
Dyskeratosis Congenita (DC) and Hoyeraal-Hreidarsson Syndrome via the DKC1 Gene
Dyskeratosis Congenita (DC) and Related Disorders Sequencing Panel with CNV Detection
Early Infantile Epileptic Encephalopathy and Rett-like Syndrome via the CDKL5 Gene
Early Infantile Epileptic Encephalopathy Sequencing Panel
Early Infantile Epileptic Encephalopathy:
Dominant and X-linked Sequencing Panel
Ehlers-Danlos Syndrome Sequencing Panel
Epilepsy and Intellectual Disability in Females via the PCDH19 Gene
Epilepsy, X-linked, with Variable Learning Disabilities and Behavior Disorders via the SYN1 Gene
Epilepsy: ALG13-Related Early Infantile Epileptic Encephalopathy via ALG13 Gene Sequencing with CNV Detection
Epilepsy: Dravet Syndrome Sequencing Panel
Epilepsy: Early Infantile Epileptic Encephalopathy via the ARHGEF9 Gene
Epilepsy: Ohtahara Syndrome Sequencing Panel
Facial Dysostosis Related Disorders Sequencing Panel
Female Infertility Sequencing Panel with CNV Detection
Fragile X Syndrome or Premature Ovarian Failure (POF1) via FMR1 CGG Repeat Expansion
Fragile X Syndrome via the FMR1 Gene
Glycogen Storage Disease and Disorders of Glucose Metabolism Sequencing Panel
Hereditary Spastic Paraplegia Comprehensive Sequencing Panel with CNV Detection
Hyperammonemia Sequencing Panel
Hyperammonemia via the OTC Gene
Hypertrophic Cardiomyopathy Sequencing Panel with CNV Detection
Intellectual Disability (Syndromic and Non-Syndromic) via HUWE1 Gene Sequencing with CNV Detection
Intellectual Disability (Syndromic and Non-Syndromic) via the UPF3B Gene
Intellectual Disability (Syndromic and Non-Syndromic) via the IQSEC2 Gene
Intellectual Disability via the ACSL4 Gene
Intellectual Disability via the PAK3 Gene
Intellectual Disability, X-linked, Claes-Jensen Type via the KDM5C Gene
Interstitial Lung Disease Sequencing Panel with CNV Detection
Joubert and Meckel-Gruber Syndromes Sequencing Panel
L1 Syndrome via the L1CAM Gene
Lesch-Nyhan Syndrome, HPRT-Related Hyperuricemia and Gout via the HPRT1 Gene
Lujan Syndrome, FG Syndrome Type 1 and Ohdo Syndrome via the MED12 Gene
Male Infertility Sequencing Panel with CNV Detection
Marfan Syndrome and Related Aortopathies Sequencing Panel
Menkes Disease and Hereditary Motor Neuropathy via the ATP7A Gene
Mental Retardation with Cerebellar Hypoplasia and Distinctive Facial Appearance via the OPHN1 Gene
Metabolic Myopathies, Rhabdomyolysis and Exercise Intolerance Sequencing Panel
Methylmalonic Aciduria and Homocystinuria Sequencing Panel
Mucopolysaccharidosis Type II via the IDS Gene
NDP-Related Vitreoretinopathies via the NDP gene
Nephrolithiasis and Nephrocalcinosis Sequencing Panel
Nephrotic Syndrome (NS)/Focal Segmental Glomerulosclerosis (FSGS) Sequencing Panel
Neurodegeneration with Brain Iron Accumulation and Infantile Neuroaxonal Dystrophy Sequencing Panel with CNV Detection
Non-syndromic Intellectual Disability (NS-ID) Sequencing Panel with CNV Detection
Nonsyndromic Hearing Loss and Deafness Sequencing Panel
Oculocerebrorenal Syndrome of Lowe (Lowe syndrome) and Dent Disease - 2 via the OCRL Gene
Oculofaciocardiodental Syndrome and Lenz Microphthalmia Syndrome via the BCOR Gene
Opitz G/BBB Syndrome Type 1 via the MID1 Gene
Pan Cardiomyopathy Sequencing Panel with CNV Detection
Parkinson Disease Sequencing Panel
Peroxisomal Disorders Sequencing Panel
Phosphoglycerate Kinase Deficiency via the PGK1 Gene
Primary Ciliary Dyskinesia (PCD)/Immotile Cilia Syndrome and Cystic Fibrosis Sequencing Panel
Primary Ciliary Dyskinesia (PCD)/Immotile Cilia Syndrome Sequencing Panel
Pure Hereditary Spastic Paraplegia Sequencing Panel with CNV Detection
Pyruvate Dehydrogenase Complex Deficiency Sequencing Panel with CNV Detection
Renpenning Syndrome via the PQBP1 Gene
Retinitis Pigmentosa (includes RPGR ORF15) Sequencing Panel with CNV Detection
Rett Syndrome via the MECP2 Gene
Rett Syndrome, Angelman Syndrome and Variant Syndromes Sequencing Panel with CNV Detection
Simpson-Golabi-Behmel Syndrome via the GPC3 Gene
Skeletal Disorders and Joint Problems Sequencing Panel with CNV Detection
Snyder-Robinson Syndrome, Spermine Synthase Deficiency via the SMS Gene
Urea Cycle Disorders Sequencing Panel
Vitreoretinopathy Sequencing Panel
Wieacker-Wolff Syndrome via the ZC4H2 Gene
X-Linked Adrenoleukodystrophy via the ABCD1 Gene
X-Linked Intellectual Disability via the CLCN4 Gene
X-linked Lenz Microphthalmia Syndrome and Lethal Ogden Syndrome via the NAA10 Gene
X-linked Lissencephaly-2 via the ARX Gene
X-linked Nance-Horan Syndrome and Congenital Cataract via the NHS Gene
X-linked Retinitis Pigmentosa (XLRP) (includes RPGR ORF15) and Choroideremia Sequencing Panel


Genetic Counselors
  • Basel-Vanagaite L. 2008. The Israel Medical Association Journal. 10: 821-6. PubMed ID: 19070297
  • de Brouwer A.P. et al. 2007. Human Mutation. 28: 207-8. PubMed ID: 17221867
  • Hu H. et al. 2016. Molecular Psychiatry. 21: 133-48. PubMed ID: 25644381
  • Human Gene Mutation Database (Bio-base).
  • Madrigal I. et al. 2007. Bmc Genomics. 8: 443. PubMed ID: 18047645
  • Mignon-Ravix C. et al. 2014. American Journal of Medical Genetics. Part A. 164A: 1991-7. PubMed ID: 24817631
  • Piton A. et al. 2013. American Journal of Human Genetics. 93: 368-83. PubMed ID: 23871722
  • Raymond F.L. 2006. Journal of Medical Genetics. 43: 193-200. PubMed ID: 16118346
  • Renieri A. et al. 2005. Journal of Cellular Physiology. 204: 8-20. PubMed ID: 15690397
  • Tarpey P.S. et al. 2009. Nature Genetics. 41: 535-43. PubMed ID: 19377476
Order Kits

Exome Sequencing with CNV Detection

Test Procedure

For the PGxome we use Next Generation Sequencing (NGS) technologies to cover the coding regions of targeted genes plus ~10 bases of non-coding DNA flanking each exon. 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 ( Common benign, likely benign, and low quality variants are filtered from analysis. All reported pathogenic, likely pathogenic, and variants of uncertain significance are confirmed by Sanger sequencing.

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

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 close to 100%, 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 most given transcripts, plus ~10 bp of flanking non-coding DNA for each exon. Unless specifically indicated, test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions, uncharacterized alternative exons, chromosomal rearrangements, repeat expansions, epigenetic effects, and mitochondrial genome variants.

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.  

In nearly all cases, our ability to determine the exact copy number change within a targeted region is limited.

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.
  • 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.


(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.


(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.


(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.
loading Loading... ×