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Test Code LAB1825 Childhood Interstitial Lung Disease (chILD) Sequencing Panel

Clinical System Name

Child Interstitial Lung Disease Seq (ILD Seq)

Description

Childhood interstitial or diffuse lung disease (chILD) is a collective term for a broad range of disorders that interfere with gas exchange in neonates, children and adolescents. They encompass rare developmental and genetic disorders that can be associated with high morbidity and mortality. Patients may present with acute respiratory failure, or more chronic symptoms including tachypnea, hypoxemia, retractions, cough, exercise intolerance and failure to thrive. Diffuse imaging abnormalities and restrictive lung physiology are frequent. The underlying pathology often is not limited to the interstitium, but involves the alveoli, airways and vasculature.

 

The Seattle Children's Hospital Molecular Laboratory offers different options for custom ILD testing:

  • Childhood Interstitial Lung Disease (chILD) Expanded Sequencing Panel

ABCA3, ACVRL1, AP3B1, ATP13A3, BMPR1B, BMPR2, CAV1, CCBE1, COPA, CSF2RA, CSF2RB, DICER1, DKC1, EIF2AK4, ELMOD2, ENG, FAT4, FGF10, FLCN, FLNA, FLT4, FOXC2, FOXF1, FOXP1, GATA2, GDF2, HPS1, HPS4, ITGA3, KCNK3, MARS1, MUC5B, NKX2-1, OAS1, PARN, RTEL1, SFTPA1, SFTPA2, SFTPB, SFTPC, SLC7A7, SMAD4, SMAD9, SMPD1, STAT3, STING1, STRA6, TBX4, TERC, TERT, TINF2

 

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

Sequencing Panel Performed TAT
ChILD Seq Panel or Single-Gene Seq Mon - Fri 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

Childhood Interstitial Lung Disease (chILD) Expanded Panel

  • 81443

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: ABCA3, ACVRL1, AP3B1, ATP13A3, BMPR1B, BMPR2, CAV1, CCBE1, COPA, CSF2RA, CSF2RB, DICER1, DKC1, EIF2AK4, ELMOD2, ENG, FAT4, FGF10, FLCN, FLNA, FLT4, FOXC2, FOXF1, FOXP1, GATA2, GDF2, HPS1, HPS4, ITGA3, KCNK3, MARS1, MUC5B, NKX2-1, OAS1, PARN, RTEL1, SFTPA1, SFTPA2, SFTPB, SFTPC, SLC7A7, SMAD4, SMAD9, SMPD1, STAT3, STING1, STRA6, TBX4, TERC, TERT, TINF2

 

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.

Clinical Utility

Timely identification of a diagnosis can direct clinical management and have important prognostic value as the outcomes of chILD are highly variable. Genetic disorders that may present with lung disease in infants and children include:

  • Developmental lung disorders (alveolar capillary dysplasia with vein misalignment, acinar dysplasia)
  • Idiopathic pulmonary hypoplasia
  • Genetic cystic lung disease
  • Genetic surfactant dysfunction disorders
  • Neuroendocrine cell hyperplasia of infancy (NEHI)
  • Idiopathic pulmonary hypertension
  • Idiopathic pulmonary hemorrhage
  • Immunodeficiencies

Requisition

Molecular Genetics

Special Instructions

Link to: UpToDate chILD