Hearing Loss NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81430, 81431

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
• Alpha-mannosidosis
• Alstrom Syndrome
• Anterior Segment Anomalies
• Auditory Neuropathy Spectrum Disorder
• Bjornstead syndrome
• Brown-Vialetto-Van Laere syndrome
• AD Cerebellar Ataxia Deafness Narcolepsy (ADCADN)
• CHARGE Syndrome
• Chudley-McCullough syndrome
• COMMAND syndrome
• Cone-Rod Dystrophy & Hearing Loss
• Congenital Deafness with Inner Ear Agenesis, Microtia, and Microdontia
• Congenital Deafness with Onychodystrophy, AD
• Craniofacial-Deafness-Hand syndrome
• D-bifunctional protein deficiency
• Deafness and Myopia
• Deafness, AD
• Deafness, AR
• Digenic Deafness, GJB2/GJB6
• Ectodermal Dysplasia/Short Stature syndrome
• Enlarged Vestibular Aqueduct
• Epstein syndrome
• Fechtner syndrome
• Heimler syndrome
• Leber Congenital Amaurosis
• Macrothrombocytopenia and Progressive Sensorineural Deafness
• Mohr-Tranebjaerg syndrome
• Nonsyndromic Deafness and Male Infertility
• PCWH syndrome
• Peripheral Neuropathy, Myopathy, Hoarsness, and Hearing Loss
• Phosphoribosylpyrophosphate Synthetase Superactivity
• Piebaldism
• Polyneuropathy, Hearing Loss, Ataxia, Retinitis Pigmentosa, and Cataract (PHARC)
• Sensorineural Node Dysfunction and Deafness
• SESAME syndrome
• Tietz Albinism-Deafness syndrome
• X-linked Deafness
• X-linked Recessive Charcot-Marie-Tooth, 5

Hearing loss comprises 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.

Next Generation Sequencing

This panel covers the coding regions of the listed nuclear genes and the flanking intronic sequences. Promoter, 3' untranslated sequences, and deep intronic sequences are also covered, but only known disease-causing variants in these regions will be reported. Targeted analysis is performed for specific variants in ten mitochondrial genes that have been associated with hearing loss; however, this does not constitute a full analysis of the mitochondrial genome (please contact the Molecular laboratory for more information). Variants identified on the panel are confirmed with Sanger sequencing if they do not meet certain quality thresholds. Large deletions and duplications (CNVs) affecting the genes of the panel can be detected; however, due to defined settings in the analysis software, CNVs smaller than 2-kb may not be identified (for example, some small exonic level copy number changes may not be identified). Please note that certain types of genetic alterations including trinucleotide repeat expansions, methylation abnormalities, and balanced rearrangements (e.g., inversions, reciprocal translocations) may not be detected by the current analysis. Due to presence of a pseudogene, analysis of the STRC gene is limited to the detection of large deletions only. If there is a concern for a sequence variant in STRC, the Molecular Laboratory offers STRC gene-specific sequencing.

The preferred sample type is 3-5ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. If saliva is submitted, and the extracted DNA is below quality control, then you will be contacted to submit a blood sample or the panel can be completed on an exome backbone. 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 where there is a known familial mutation. Additional fees for cell culture and maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.