Hearing Loss NGS Panel

This panel of 91 genes is intended for patients with a diagnosis of Hearing Loss and is performed by Next Generation Sequencing (NGS). This molecular test is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Turnaround Time

8 weeks

CPT Code(s)

81430

Cost

$3,500

Genes

• Aminoglycoside-induced hearing loss
• Alport syndrome
• Branchiootorenal syndrome
• Baraitser-Winter syndrome
• Deafness-infertility syndrome
• Dominant nonsyndromic deafness (DFNA)
• Jervell and Lange-Nielsen syndrome
• Pendred syndrome
• Perrault syndrome
• Recessive non syndromic deafness (DFNB)
• Renal tubular acidosis
• Mitochondrial Nonsyndromic Sensorineural Deafness
• Stickler syndrome
• Usher syndrome
• Waardenburg syndrome
• Wolfram syndrome
• Otospondylomegaepiphyseal dysplasia
• Bartter syndrome
• Sinoatrial node dysfunction and deafness
• Fibrochondrogenesis
• Weissenbacher-Zweymuller syndrome
• Otofaciocervical syndrome
• Bart-Pumphrey syndrome
• Hystrix-like ichthyosis with deafness
• Keratitis-ichthyosis-deafness syndrome
• Palmoplantar keratoderma with deafness
• Vohwinkel syndrome

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. List of Genes and Associated Clinical Phenotypes

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. 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. 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.

• Aminoglycoside-Induced Hearing Loss: MT-RNR1 Targeted Analysis
• Connexin 26: GJB2 Sequencing
• Connexin 26: GJB2 Targeted Mutation Analysis
• CytoScan Xon Microarray: 2-10 Genes
• QUICK Analysis

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.