Hermansky-Pudlak Syndrome & Pulmonary Fibrosis NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81443

Cost

$3,000

Genes

• Hermansky-Pudlak syndrome
• Idiopathic pulmonary fibrosis
• Dyskeratosis congenita
• Pulmonary surfactant metabolism dysfunction
• Autoimmune interstitial lung, joint, and kidney disease
• Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis
• Ectodermal Dysplasia/Short Stature syndrome
• LIG4 syndrome
• Dubowitz syndrome
• Interstitial lung and liver disease
• Pediatric pulmonary alveolar proteinosis
• Choreoathetosis hypothyroidism and neonatal respiratory distress
• Telomere-related Pulmonary fibrosis and/or bone marrow failure
• Susceptibility to chronic obstructive pulmonary disease
• STING-associated vasculopathy with onset in infancy
• Poikiloderma with neutropenia
• Rothmund-Thomson syndrome
• Neurodevelopmental disorder with brain, liver, and lung abnormalities

Primary features include hypopigmentation of the hair, skin, and eyes, nystagmus, and associated visual impairment. In addition to the pigmentation findings, individuals with Hermanksy-Pudlak may also have prolonged bleeding times and easy bruising, kidney failure, and bowel disorders. Pulmonary fibrosis caused by scarring of lung tissue may also be present, and symptoms include shortness of breath and a dry cough leading to death from respiratory failure within a few years without effective treatment.

Next Generation Sequencing

The current design of this panel covers all genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. Novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.