Comprehensive Hearing Loss and Deafness Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: EA0501

The Blueprint Genetics Comprehensive Hearing Loss and Deafness Panel is a 158 gene test for genetic diagnostics of patients with clinical suspicion of Alport syndrome, branchio-oto-renal (BOR) syndrome, non-syndromic genetic deafness, Pendred syndrome, sensorineural hearing loss, unilateral and bilateral, Stickler syndrome, Usher syndrome or Waardenburg syndrome.

Hearing loss is a genetically and clinically heterogenous group of diseases and syndromes and may be classified in several different ways. This Panel includes comprehensively genes associated with both syndromic and non-syndromic hearing loss. In addition to protein coding regions, two disease causing intronic variants of HGF gene are targeted in this Panel. Inheritance of these disorders may be autosomal recessive or dominant as well as X-linked. This comprehensive Panel includes Waardenburg Syndrome Panel, Pendred Syndrome Panel, Usher Syndrome Panel, Stickler Syndrome Panel, Alport Syndrome Panel, Branchio-Oto-Renal Panel, Syndromic Hearing Loss Panel and Non-Syndromic Hearing Loss Panel.

About Hearing Loss and Deafness

Hearing loss is a genetically very heterogenous group of phenotypes varying in severity and causes. Non-syndromic sensorineural hearing loss is a partial or total loss of hearing that occurs in isolation, without other associated medical disorders. In syndromic hearing loss, symptoms affecting other parts of the body occur interlinked with hearing impairnment or deafness. Sensorineural hearing loss can be unilateral or bilateral and it can be stable or progressive. In addition, the loss may appear with various intensivity to high, middle or low tones. Some 75%-to-85% of congenital hereditary hearing impairnment have non-syndromic origin, while the remaining 15%-to-25% is syndromic in origin. The prevalence of non-syndromic hearing loss is 3-4:10000 neonates and increases with age. In many populations, mutations in GJB2 are the most prevalent explaining up to 50% of all non-syndromic hearing losses. Altogether syndromic hearing loss accounts for 20% to 30% of congenital hearing loss and deafness and the combined prevalence of syndromic hearing loss is approximately 1-2:10000.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Comprehensive Hearing Loss and Deafness Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ABHD12Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataractAR1015
ACTG1*Deafness, Baraitser-Winter syndromeAD1737
ADCY1DeafnessAR11
ADGRV1Usher syndromeAR/Digenic43153
ALMS1*Alström syndromeAR31281
ANKHCalcium pyrophosphate deposition disease (familial chondrocalcinosis type 2), Craniometaphyseal dysplasia autosomal dominant typeAD1221
ATP6V1B1Renal tubular acidosis with deafnessAR839
BCS1LBjornstad syndromeAR2032
BDP1*Hearing lossAD/AR1
BSNDSensorineural deafness with mild renal dysfunction, Bartter syndromeAR1021
BTDBiotinidase deficiencyAR165231
CABP2DeafnessAR16
CACNA1DPrimary aldosteronism, seizures, and neurologic abnormalities, Sinoatrial node dysfunction and deafnessAD/AR45
CCDC50DeafnessAD13
CD151Raph blood groupBG14
CDH23Deafness, Usher syndromeAR/Digenic48294
CDKN1CBeckwith-Wiedemann syndrome, IMAGE syndromeAD2579
CEACAM16DeafnessAD33
CHD7Isolated gonadotropin-releasing hormone deficiency, CHARGE syndromeAD128746
CHSY1Temtamy preaxial brachydactyly syndromeAR610
CIB2Deafness, Usher syndromeAR415
CLDN14DeafnessAR811
CLIC5DeafnessAR11
CLRN1Retinitis pigmentosa, Usher syndromeAR1432
COCHDeafnessAD1027
COL2A1Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1AD106537
COL4A3Alport syndromeAD/AR17225
COL4A4Alport syndromeAD/AR17170
COL4A5Alport syndromeXL627909
COL4A6Deafness, with cochlear malformationXL124
COL9A1Stickler syndrome recessive type, Multiple epiphyseal dysplasia type 6 (EDM6)AR34
COL9A2Stickler syndrome, Multiple epiphyseal dysplasia type 2 (EDM2)AR512
COL9A3Multiple epihyseal dysplasia type 3 (EDM3)AD316
COL11A1Marshall syndrome, Fibrochondrogenesis, Stickler syndrome type 2AD/AR1876
COL11A2Weissenbacher-Zweymuller syndrome, Deafness, Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non-ocular)AD/AR1751
CRYMDeafnessAD23
DCDC2DeafnessAR411
DFNA5DeafnessAD68
DFNB31Deafness, Usher syndromeAR928
DFNB59DeafnessAR719
DIABLODeafnessAD12
DIAPH1DeafnessAD412
DIAPH3Non-syndromic sensorineural deafnessAD/AR16
DLX5Split-hand/foot malformation with sensorineural hearing lossAR38
DSPPDentin dysplasia, Dentinogenesis imperfecta, Deafness, with dentinogenesis imperfectaAD848
EDN3Hirschsprung disease, Central hypoventilation syndrome, congenital, Waardenburg syndromeAD/AR621
EDNRBHirschsprung disease, ABCD syndrome, Waardenburg syndromeAD/AR562
ELMOD3DeafnessAR11
EPS8DeafnessAR12
ESPN*DeafnessAD/AR711
ESRRBDeafnessAR816
EYA1Otofaciocervical syndrome, Branchiootic syndrome, Branchiootorenal syndromeAD33186
EYA4Dilated cardiomyopathy (DCM)AD822
FAM65BDeafnessAR11
FGF3Deafness, congenital with inner ear agenesis, microtia, and microdontiaAR1220
FGFR3Lacrimoauriculodentodigital syndrome, Muenke syndrome, Crouzon syndrome with acanthosis nigricans, Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome, Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia type 1, Thanatophoric dysplasia type 2, SADDANAD/AR4768
FOXI1Pendred syndrome, Enlarged vestibular aqueductAR18
GATA3Hypomagnesemia, renalAD1677
GIPC3DeafnessAR917
GJB2Deafness, Bart-Pumphrey syndrome, Keratoderma, palmoplantar, with deafness, Vohwinkel syndrome, Hystrix-like ichthyosis with deafness, Keratitis-icthyosis-deafness syndromeAD/AR/Digenic96385
GJB3DeafnessAD/Digenic837
GJB6DeafnessAR/Digenic828
GPSM2Deafness, Chudley-McCullough syndromeAR1011
GRHL2Ectodermal dysplasia/short stature syndromeAD/AR66
GRXCR1DeafnessAR49
GRXCR2DeafnessAR11
HARSUsher syndromeAR610
HGFDeafnessAR412
HOMER2DeafnessAD22
HOXB1Facial paresis, hereditary congenitalAR15
HSD17B4Perrault syndromeAR1886
ILDR1DeafnessAR422
KARSCharcot-Marie-Tooth diseaseAR614
KCNE1Long QT syndrome, Jervell and Lange-Nielsen syndromeAD/AR/Digenic646
KCNJ10Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome), Pendred syndrome, Enlarged vestibular aqueductAR/Digenic1426
KCNQ1Short QT syndrome, Long QT syndrome, Atrial fibrillation, Jervell and Lange-Nielsen syndromeAD/AR/Digenic237590
KCNQ4DeafnessAD2435
LHFPL5DeafnessAR410
LOXHD1DeafnessAR1237
LRP2Donnai-Barrow syndrome, Faciooculoacousticorenal syndromeAR1528
LRTOMTDeafnessAR616
MANBAMannosidosis, lysosomalAR918
MARVELD2DeafnessAR615
METDeafness, Renal cell carcinoma, papillaryAD/AR1323
MIR96DeafnessAD24
MITFRenal cell carcinoma with or without malignant melanoma, Tietz albinism-deafness syndrome, Waardenburg syndrome, Melanoma, cutaneous malignantAD1550
MSRB3DeafnessAR42
MYH9Sebastian syndrome, May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, Macrothrombocytopenia and progressive sensorineural deafnessAD19113
MYH14Deafness, Peripheral neuropathy, myopathy, hoarseness, and hearing lossAD626
MYO1ADeafnessAD116
MYO3ADeafnessAR618
MYO6DeafnessAR1447
MYO7ADeafness, Usher syndromeAR125402
MYO15ADeafnessAR48209
NARS2Combined oxidative phosphorylation deficiencyAR36
NDPExudative vitreoretinopathy, Norrie diseaseXL25155
NLRP3Neonatal onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome, Chronic infantile neurologic cutaneous articular (CINCA) syndromeAD15125
OSBPL2DeafnessAD23
OTOA*DeafnessAR1224
OTOFNeuropathy, DeafnessAR94153
OTOGDeafnessAR53
OTOGLDeafnessAR1017
P2RX2DeafnessAD23
PAX3Craniofacial-deafness-hand syndrome, Waardenburg syndromeAD/AR20135
PCDH15Deafness, Usher syndromeAR/Digenic2897
PDZD7Usher syndromeDigenic114
PNPT1*DeafnessAR124
POLR1CTreacher Collins syndromeAR1318
POLR1DTreacher Collins syndromeAD/AR725
POU3F4DeafnessXL1966
POU4F3DeafnessAD614
PRPS1*Deafness, Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndromeXL2226
PTPRQDeafnessAR527
RDX*DeafnessAR57
RMND1*Combined oxidative phosphorylation deficiencyAR1313
RPS6KA3Coffin-Lowry syndrome, Mental retardationXL35161
SALL4Acro-renal-ocular syndrome, Duane-radial ray/Okohiro syndromeAD1548
SEMA3ECHARGE syndromeAD13
SERPINB6DeafnessAR13
SIX1Deafness, Branchiootic syndrome, Branchiootorenal syndromeAD915
SIX5Branchiootorenal syndromeAD37
SLC17A8DeafnessAD15
SLC19A2Thiamine-responsive megaloblastic anemia syndromeAR1047
SLC26A4Deafness, Pendred syndrome, Enlarged vestibular aqueductAR98521
SLC26A5DeafnessAR27
SLC29A3Histiocytosis-lymphadenopathy plus syndrome, DysosteosclerosisAR1722
SLC33A1*Congenital cataracts, hearing loss, and neurodegenerationAR67
SLITRK6Deafness and myopiaAR33
SMAD4Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasiaAD119128
SMPXDeafnessXL59
SNAI2Waardenburg syndromeAR24
SOX10Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung diseaseAD31119
STRC*DeafnessAR2471
SUCLA2Mitochondrial DNA depletion syndromeAR826
SUCLG1Mitochondrial DNA depletion syndromeAR1228
SYNE4DeafnessAR41
TBC1D24Deafness, Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndromeAD/AR2741
TCOF1Treacher Collins syndromeAD17303
TECTADeafnessAD/AR1797
TFAP2ABranchiooculofacial sydromeAD942
TIMM8A*Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve atrophy with dementiaXL1121
TJP2Cholestasis, progressive familial intrahepatic, Hypercholanemia, familialAR1515
TMC1DeafnessAR2384
TMC2Hearing lossAD/AR
TMEM132EHearing lossAD/AR1
TMIEDeafnessAR810
TMPRSS3DeafnessAR2066
TNCDeafnessAD25
TPRNDeafnessAR510
TRIOBPDeafnessAR1332
TRMULiver failure, infantile, Reversible infantile respiratory chain deficiencyAR1216
TSPEARDeafnessAR18
TYR*Albinism, oculocutaneousAR46356
USH1CDeafness, Usher syndromeAR1345
USH1GUsher syndromeAR924
USH2AUsher syndromeAR147924
VCANWagner diseaseAD1119
WFS1Wolfram syndromeAR59343
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive hearing loss and deafness panel that covers classical genes associated with Alport syndrome, branchio-oto-renal (BOR) syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Mohr-Tranebjaerg syndrome, non-syndromic genetic deafness, Norrie disease, Pendred syndrome, sensorineural hearing loss, unilateral and bilateral, Stickler syndrome, treacher Collins syndrome, Usher syndrome and Waardenburg syndrome. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81430
DEL/DUP81431


ICD codes

Commonly used ICD-10 codes when ordering the Comprehensive Hearing Loss and Deafness Panel

ICD-10Disease
E70.3Waardenburg syndrome
Q87.8Alport syndrome
H90.5Sensorineural hearing loss, unilateral and bilateral
E07.1Pendred syndrome
H35.50Usher syndrome
Q87.5Stickler syndrome
Q87.8Branchio-oto-renal (BOR) syndrome

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.