NGS Hearing Loss Panel
|Disorder||Hearing Loss, Deafness|
|Clinical info||Hearing loss composes a very heterogeneous group of diagnoses and is one of the most common findings at birth, affecting about 1 in every 500 newborns with the prevalence increasing with age, (Morton & Nance 2006). Deafness is often categorized and described based on 3 key components: conductive versus sensorineural, syndromic or nonsyndromic, and prelingual or postlingual. While some hearing loss can be environmental, multifactorial, more than 50% of prelingual deafness is attributed to genetic causes.
With a large proportion of deafness due genetics and significant genetic heterogeneity, it is important to have an efficient and comprehensive testing option for patients. Identifying the underlying molecular etiology of the hearing loss has important implications for the patients and their families. A specific diagnosis can provide prognostic insights and guide treatment of the hearing loss as well as facilitate monitoring for additional associated health concerns. A clear diagnosis also prevents further, unnecessary testing and gives valuable recurrence risk information.
For patients with a specific suspected disorder, individual gene sequencing should be considered first.
Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.
The current design of the Hearing Loss Panel v3 covers the coding region for 91 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. THe remaining two genes are a targeted analysis. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All 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 if applicable. 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 testing whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.
Effective January 1, 2017, all NGS panels are performed on an exome backbone with the potential for reflex to whole exome sequencing at a reduced cost. Please contact the laboratory to discuss the requirements for exome sequencing.
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml.|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. 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.|
|Turnaround time||8-10 weeks|
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.
Insurance billing is available for this test. The Insurance Billing Form is required along with copies of the authorization or letter of agreement from the insurance company.
Molecular Diagnostic Lab
The Molecular Diagnostic Lab offers DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, MLPA deletion/duplication testing, trinucleotide repeat analysis and next generation sequencing panels.