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Test Code LAB1866 Intestinal Pseudo-Obstruction Sequencing Panel

Clinical System Name

Intestinal Pseudo-Obstruction Seq

Description

Chronic intestinal pseudo-obstruction (IPO) is a rare disorder characterized by abnormalities affecting peristalsis - the involuntary, coordinated muscular contractions of the gastrointestinal (GI) tract. Peristalsis moves material through the digestive system under the control of nerves, pacemaker cells, and hormones. When peristalsis is altered or inefficient, normal nutritional requirements cannot be met and may lead to unintended weight loss, malnourishment, and even severe, life-threatening complications. Altered peristalsis may be caused by a physical blockage (i.e. an obstruction). Alternatively, it may be caused by abnormalities relating to the muscles within the GI tract (visceral myopathy), or abnormalities relating to nerves within the GI tract (visceral neuropathy), collectively referred to as pseudo-obstruction. Several genetic causes of IPO have been identified where IPO may be a major or minor feature.

  • Intestinal Pseudo-Obstruction Full Sequencing Panel

The reported gene set in this full panel includes: ACTA2, ACTG2, CHD8, CLMP, ERBB3, FLNA, LIG3, LMOD1, MYH11, MYL9, MYLK, POLG, POLG2, RAD21, SGO1, TYMP

 

  • Additional testing options - we offer the following additional options for custom IPO syndrome testing:
    • Single-gene sequencing When there is strong clinical suspicion, any gene listed on the IPO Full Sequencing Panel is available as a single-gene sequencing test.
    • Reflex to IPO Full Sequencing Panel The option to reflex to the IPO Full Sequencing Panel when the single-gene test  is non-diagnostic.

 

Please contact LabGC@seattlechildrens.org if you would like to order reflexive testing after the original testing report has been issued.

 

Sample Requirements

Samples MUST have two of the following to be accepted as properly labeled: first & last name, outside medical record number, unique accession number, or date of birth.

 

Note: For patients who have had a whole blood transfusion, wait 10 days post transfusion to draw for genetic testing. No wait time is necessary for blood or saliva collection if the patient received leuko-reduced red cells or plasma.

 

Specimen: Whole blood

Container(s): Lavender/EDTA

Preferred Vol: 3 mL

Minimum Vol: 1 mL

Note: Heparin samples (Green tops) are unacceptable.

 

Specimen: Saliva collected using Oragene Dx OGD-575/675 collection kit.

Container: Oragene Dx OGD-575/675 collection kit

IMPORTANT NOTE: Manufacturer instructions must be followed. The Oragene Dx OGD575/675 kit is not for children under 6 months. Contact the lab directly for more information or to obtain a kit - 206-987-2617

 

Specimen: Extracted DNA (MUST specify source on requisition)

Preferred: 5 mcg

Minimum: 2 mcg

Note: Isolation of nucleic acids for clinical testing must be performed in a CLIA-certified
laboratory or a laboratory meeting equivalent requirements as determined by the CAP
and/or the CMS. DNA concentration minimum 50 µg/mL; 260/280 ratio 1.70-2.00.

Processing Instructions

Specimen Type Description

Temperature

 Storage instructions
Whole blood EDTA or ACD tube Refrigerate Molecular Genetics box in CPA refrigerator #2
Extracted DNA DNA aliquot tube Refrigerate Molecular Genetics box in CPA refrigerator #2
Saliva OGD-575/675 kit Room Temp Place in CPA Cytogenetics room temp box with requisition

Off-site collection: Refrigerate blood samples until ready to ship.  Transport blood, saliva, or DNA at room temperature via overnight shipping.

Stability

Specimen Type Temperature Time
Whole blood, extracted DNA RT 3-5 d
Whole blood, extracted DNA 2 - 8 C

7 d

Saliva, extracted from ORAgene Dx OGD-575/675

 Room temperature or refrigerated up to 2 weeks
Extracted DNA -20 C or -70 C  years

Note: Whole blood samples > 7days may be submitted to be assessed by our lab for acceptability for testing.

Availability

STAT Performed TAT
Contact lab Monday - Friday 4-6 weeks

Performing Laboratory

Seattle Children's Laboratory

Department

Department:  Molecular Genetics Laboratory

Phone: 206-987-3872

Lab Client Services: 206-987-2617

Lab Genetic Counselor: LabGC@seattlechildrens.org

CPT Codes

81479

Methodology

Method: Next Generation Sequencing technology using an Illumina NextSeq instrument. Target region includes coding exons and a minimum of 10 bp of flanking intron boundaries of the genes tested. Target enrichment performed using a custom Integrated DNA Technologies (IDT) Exome Hyb Panel v2.

 

Average coverage ~150x, depth of coverage for all target regions is at least 20x.

 

Reported gene set: ACTA2, ACTG2, CHD8, CLMP, ERBB3, FLNA, LIG3, LMOD1, MYH11, MYL9, MYLK, POLG, POLG2, RAD21, SGO1, TYMP

 

Limitations:

This testing is performed on an exome backbone with analysis restricted to the panel genes. This method can detect single nucleotide variants (SNVs), small deletions, small insertions, and copy number variants in the regions targeted. Some regions cannot be efficiently captured due to sequence homology or sequence properties. This method will not detect large insertions and deletions, complex indels, structural variants (e.g. inversions, translocations), short tandem repeats, or other complex variants. Variants located outside of targeted regions will not be detected.

 

Based on validation studies, the bioinformatics pipeline showed precision and detection >99% for SNVs in regions with coverage greater than 20x and high mapping quality. Sensitivity for CNVs involving multiple genes is >99% and sensitivity for intragenic CNVs is >90%. Mosaic sequence variants present at <25% allele frequency may not be reliably detected, and detection sensitivity is dependent on the nature of the variant. The sensitivity of detection of mosaic copy number variants has not been evaluated.

Reference Range

Interpretive report will be provided. Variants are not reported if they are considered benign.

References

Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome Overview GeneReviews 

ACTG2 Visceral Myopathy GeneReviews  

Mitochondrial Neurogastrointestinal Encephalopathy Disease GeneReviews

Clinical Utility

Intestinal pseudo-obstruction (IPO) may be suspected in patients with abdominal pain and distention, nausea, vomiting, and constipation or diarrhea. Other features may include include urinary retention, liver failure, hypotonia or spasticity, ophthalmoplegia, recurrent infections, intellectual disability, seizures, or dysmorphic facial features. A genetic cause of IPO may be suspected in patients with a clinical diagnosis of:

  • Megacystis-microcolon-intestinal hypoperistalsis syndrome
  • Multisystemic smooth muscle dysfunction syndrome
  • Congenital short bowel syndrome
  • Visceral myopathy
  • Mitochondrial disease
  • Progressive external ophthalmoplegia
  • Mitochondrial DNA depletion syndrome-1
  • Mitochondrial neurogastrointestinal encephalopathy
  • Mungan syndrome
  • Chronic atrial and intestinal dysrhythmia
  • Periventricular nodular heterotopias
  • Pyloric stenosis
  • Intestinal malrotation
  • Slow-transit constipation

Requisition

Molecular Genetics