Collect

2 purple-top (EDTA) tubes whole blood. Saliva is also acceptable.


 

Specimen Preparation

Please provide detailed clinical history and features. Parental samples can be submitted for DNA extraction at no-cost. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@email.chop.edu
 

Storage/Transport Temperature

Room temperature

Volume Required

5 mL in each tube

Minimum Required

3 mL

Phlebotomy Draw

Yes

Methodology

CHOP VEO-IBD Panel In is performed using the Agilent SureSelect XT Clinical Research Exome kit (per manufacturer’s protocol) followed by next generation sequencing on the Illumina HiSeq 2000 or 2500 platform with 100bp paired-end reads and an average sequencing depth of 100X. Mapping and analysis are based on the human genome build UCSC hg19 reference sequence. Variant calls, filtration and annotations are generated using an in-house custom-built bioinformatics pipeline. Sanger sequencing is used to fill in regions with insufficient coverage and to confirm all clinically significant variants, when appropriate. However, certain technically challenging, low coverage regions will not be filled in.
Detection of IKBKG variants utilizes Long-Range PCR Amplification (LR-PCR) followed by NGS sequencing. Deletion/duplication analysis is performed using a validated algorithm that utilizes coverage information from exome sequencing data to infer exon-level copy number variants, which when identified will be confirmed by custom digital droplet PCR (ddPCR) or another appropriate method before reporting.
 

Reported

42 days

Synonyms

  • IBDPN
  • VEOIBD
  • VEO-IBD
  • VEO
  • IBD
  • CHOP IBD panel
  • CHOP VEO panel
  • CHOP VEOIBD panel

LIS Mnemonic

IBDPN

Performed By

Division of Genomic Diagnostics

Available STAT

No

Test Notes

Exome-wide capture of the coding regions and splice sites (±10bp) of the genes on the CHOP VEO-IBD Panel In is performed using the Agilent SureSelect XT Clinical Research Exome kit (per manufacturer’s protocol) followed by next generation sequencing on the Illumina HiSeq 2000 or 2500 platform with 100bp paired-end reads and an average sequencing depth of 100X. Mapping and analysis are based on the human genome build UCSC hg19 reference sequence. Variant calls, filtration and annotations are generated using an in-house custom-built bioinformatics pipeline. Sanger sequencing is used to fill in regions with insufficient coverage and to confirm all clinically significant variants, when appropriate. However, certain technically challenging, low coverage regions will not be filled in.
Detection of IKBKG variants utilizes Long-Range PCR Amplification (LR-PCR) followed by NGS sequencing. Deletion/duplication analysis is performed using a validated algorithm that utilizes coverage information from exome sequencing data to infer exon-level copy number variants, which when identified will be confirmed by custom digital droplet PCR (ddPCR) or another appropriate method before reporting.
 

Clinical Features

Inflammatory bowel disease (IBD) is caused by defects in the intestinal mucosal barrier and inappropriate immune responses toward the intestinal bacterial microbiota which lead to chronic inflammation. This inflammation can result in diarrhea, bloody stools, abdominal pain, growth failure, and weight loss. Very early onset IBD (VEO-IBD), refers to disease onset in children less than 6 years in age and is commonly caused by highly penetrant monogenic variants in over 50 genes. These conditions can be caused by de novo alterations, or can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern.
The CHOP very early onset inflammatory bowel disease (VEO-IBD) is indicated for any patient with IBD in whom:
1) A monogenetic cause is suspected but not yet identified
2) Children with disease onset before the age of 6 years
3) No other obvious and well-established complex genetic, environmental, or other non-genetic factors causative of IBD are present
4) No other major clinical features associated with specific known syndromes are present
 

Detection Rate

The diagnostic yield for comprehensive next generation sequencing panels is not yet well-established, and depends on the panel’s gene content and the patient’s clinical features. However, in a study of 22 children with VEO-IBD, sequencing of 40 genes associated with this condition resulted in a positive rate of 18% [Kammermeier 2014, PMID: 25194001].
 

Utility

The clinical utility of the assay is to inform a clinical diagnosis of VEO-IBD, inform medical treatment decisions, facilitate genetic counseling, inform recurrence risk assessment, and support testing of at-risk family members.
 

Molecular Testing Notes

The CHOP VEO-IBD Panel focuses on genes associated with non-syndromic or “apparent” non-syndromic VEO-IBD. This panel includes the following 98 genes: ADA, ADAM17, AICDA, AIRE, ARPC1B, BTK, CD19, CR2, CD40, CD40LG, CD81, CHD7, CIITA, COL7A1, CTLA4, CYBA, CYBB, DCLRE1C, DKC1, DOCK8, FERMT1, FOXP3, FUT2, G6PC3, HPS1, HPS4, HPS6, ICOS, IKBKB, IKBKG, IKZF1, IL10, IL10RA, IL10RB, IL21, IL23R, IL2RA, IL2RG, IL7R, ITCH, ITGB2, ITK, LCK, LIG4, LRBA, LYST, MALT1, MEFV, MVK, MYO5A, NCF2, NCF4, NFAT5, NFKB1, NFKB2, NLRC4, NLRP12, NOP10, PIK3R1, PRF1, PLCG2, PTEN, RAB27A, RAC1, RAC2, RAG1, RAG2, RET, RFX5, RFXANK, RFXAP, RTEL1, SH2D1A, SKIV2L, SLC37A4, STAT1, STAT3, STAT5A, STAT5B, STX3, STXBP2, STXBP3, TAP1, TAP2, TERC, TERT, TINF2, TNFAIP3, TNFAIP6, TNFRSF13B, TRAF3, TTC37, TTC7A, UNC13D, UNG, WAS, XIAP, ZAP70.
 

CPT Codes

81404x2, 81405, 81406x4, 81407, 81479
Collection

Collect

2 purple-top (EDTA) tubes whole blood. Saliva is also acceptable.


 

Specimen Preparation

Please provide detailed clinical history and features. Parental samples can be submitted for DNA extraction at no-cost. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@email.chop.edu
 

Storage/Transport Temperature

Room temperature

Volume Required

5 mL in each tube

Minimum Required

3 mL

Phlebotomy Draw

Yes
Ordering

Methodology

CHOP VEO-IBD Panel In is performed using the Agilent SureSelect XT Clinical Research Exome kit (per manufacturer’s protocol) followed by next generation sequencing on the Illumina HiSeq 2000 or 2500 platform with 100bp paired-end reads and an average sequencing depth of 100X. Mapping and analysis are based on the human genome build UCSC hg19 reference sequence. Variant calls, filtration and annotations are generated using an in-house custom-built bioinformatics pipeline. Sanger sequencing is used to fill in regions with insufficient coverage and to confirm all clinically significant variants, when appropriate. However, certain technically challenging, low coverage regions will not be filled in.
Detection of IKBKG variants utilizes Long-Range PCR Amplification (LR-PCR) followed by NGS sequencing. Deletion/duplication analysis is performed using a validated algorithm that utilizes coverage information from exome sequencing data to infer exon-level copy number variants, which when identified will be confirmed by custom digital droplet PCR (ddPCR) or another appropriate method before reporting.
 

Reported

42 days

Synonyms

  • IBDPN
  • VEOIBD
  • VEO-IBD
  • VEO
  • IBD
  • CHOP IBD panel
  • CHOP VEO panel
  • CHOP VEOIBD panel

LIS Mnemonic

IBDPN

Performed By

Division of Genomic Diagnostics

Available STAT

No

Test Notes

Exome-wide capture of the coding regions and splice sites (±10bp) of the genes on the CHOP VEO-IBD Panel In is performed using the Agilent SureSelect XT Clinical Research Exome kit (per manufacturer’s protocol) followed by next generation sequencing on the Illumina HiSeq 2000 or 2500 platform with 100bp paired-end reads and an average sequencing depth of 100X. Mapping and analysis are based on the human genome build UCSC hg19 reference sequence. Variant calls, filtration and annotations are generated using an in-house custom-built bioinformatics pipeline. Sanger sequencing is used to fill in regions with insufficient coverage and to confirm all clinically significant variants, when appropriate. However, certain technically challenging, low coverage regions will not be filled in.
Detection of IKBKG variants utilizes Long-Range PCR Amplification (LR-PCR) followed by NGS sequencing. Deletion/duplication analysis is performed using a validated algorithm that utilizes coverage information from exome sequencing data to infer exon-level copy number variants, which when identified will be confirmed by custom digital droplet PCR (ddPCR) or another appropriate method before reporting.
 

Clinical Features

Inflammatory bowel disease (IBD) is caused by defects in the intestinal mucosal barrier and inappropriate immune responses toward the intestinal bacterial microbiota which lead to chronic inflammation. This inflammation can result in diarrhea, bloody stools, abdominal pain, growth failure, and weight loss. Very early onset IBD (VEO-IBD), refers to disease onset in children less than 6 years in age and is commonly caused by highly penetrant monogenic variants in over 50 genes. These conditions can be caused by de novo alterations, or can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern.
The CHOP very early onset inflammatory bowel disease (VEO-IBD) is indicated for any patient with IBD in whom:
1) A monogenetic cause is suspected but not yet identified
2) Children with disease onset before the age of 6 years
3) No other obvious and well-established complex genetic, environmental, or other non-genetic factors causative of IBD are present
4) No other major clinical features associated with specific known syndromes are present
 

Detection Rate

The diagnostic yield for comprehensive next generation sequencing panels is not yet well-established, and depends on the panel’s gene content and the patient’s clinical features. However, in a study of 22 children with VEO-IBD, sequencing of 40 genes associated with this condition resulted in a positive rate of 18% [Kammermeier 2014, PMID: 25194001].
 

Utility

The clinical utility of the assay is to inform a clinical diagnosis of VEO-IBD, inform medical treatment decisions, facilitate genetic counseling, inform recurrence risk assessment, and support testing of at-risk family members.
 

Molecular Testing Notes

The CHOP VEO-IBD Panel focuses on genes associated with non-syndromic or “apparent” non-syndromic VEO-IBD. This panel includes the following 98 genes: ADA, ADAM17, AICDA, AIRE, ARPC1B, BTK, CD19, CR2, CD40, CD40LG, CD81, CHD7, CIITA, COL7A1, CTLA4, CYBA, CYBB, DCLRE1C, DKC1, DOCK8, FERMT1, FOXP3, FUT2, G6PC3, HPS1, HPS4, HPS6, ICOS, IKBKB, IKBKG, IKZF1, IL10, IL10RA, IL10RB, IL21, IL23R, IL2RA, IL2RG, IL7R, ITCH, ITGB2, ITK, LCK, LIG4, LRBA, LYST, MALT1, MEFV, MVK, MYO5A, NCF2, NCF4, NFAT5, NFKB1, NFKB2, NLRC4, NLRP12, NOP10, PIK3R1, PRF1, PLCG2, PTEN, RAB27A, RAC1, RAC2, RAG1, RAG2, RET, RFX5, RFXANK, RFXAP, RTEL1, SH2D1A, SKIV2L, SLC37A4, STAT1, STAT3, STAT5A, STAT5B, STX3, STXBP2, STXBP3, TAP1, TAP2, TERC, TERT, TINF2, TNFAIP3, TNFAIP6, TNFRSF13B, TRAF3, TTC37, TTC7A, UNC13D, UNG, WAS, XIAP, ZAP70.
 
Result Interpretation
Administrative

CPT Codes

81404x2, 81405, 81406x4, 81407, 81479