Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Remarks
This analysis includes sequencing and copy number analysis of the genes known to cause nonsyndromic sensorineural hearing loss (NSHL) as well as some syndromic hearing loss that may initially present like NSHL.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Clinical Features
Hearing loss is the most prevalent sensory perception deficit disorder in humans, affecting about 1 in 500 newborns, and a genetic etiology is suspected in more than 60% of patients. Hearing loss can be classified as non-syndromic (70%) or syndromic (30%) based on the presence or absence of other associated clinical features.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday-Friday 9:00am - 4:00pm
Reported
42 days
Detection Rate
The Comprehensive AUDIOME panel is intended for the diagnosis of non-syndromic hearing loss (NSHL) and some types of syndromic hearing loss that may initially present as NSHL. This panel includes the examination of sequence variants and copy number variants of the genes listed in the 'Molecular Testing Notes' section and known to cause non-syndromic, syndromic, and both non-syndromic and syndromic hearing loss. Additionally, the testing includes targeted analysis of the MT-RNR1 m.1555A>G (associated with hearing loss following aminoglycoside exposure) and MT-TS1 m.7445A>G (associated with childhood onset sensorineural hearing loss) variants. Isolated CATSPER2 homozygous deletions (without STRC involvement) will not be reported. This analysis may not identify certain types of variants, such as mosaicism, some copy number variants, structural variants, repeat expansions or other long segments of repetitive DNA sequences, some novel variants in the non-coding regions that could affect gene expression (apart from splice site variants) unless specified above. In addition, technically difficult regions (including those that are GC-rich or have high homology) might not be sequenced by this test. The detection limit is 20% for heteroplasmic MT-RNR1 m.1555A>C and MT-TS1 m.7445 A>C variants. A negative result does not exclude the possibility that a proband harbors a pathogenic variant that was undetectable by this test due to the technical limitations. The analysis was dependent on current scientific knowledge of genetic disease at the time of the analysis. Clinical implications of some variants may be uncertain or unknown at the time of this report and may change over time. Interpretations are made with the assumption that any clinical information and family relationships provided to the laboratory are accurate. Please note, this analysis is not designed to report risk alleles for multi-factorial/complex disease or genetic variants implicated in complex disease via genome wide association studies.
Utility
The clinical utility of the assay is to support a clinical diagnosis of hearing loss related phenotypes, facilitate genetic counseling, and assess the risk to first-degree relatives as well as other at-risk family members.
Synonyms
Comprehensive AUDIOME, hearing loss panel, deafness
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis are based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants. Long range polymerase chain reaction (LR-PCR) for STRC is performed followed by next generation sequencing. Copy number variants in the STRC (NM_153700.2) and CATSPER2 (NM_172095.4) loci are determined by droplet digital PCR (ddPCR) assays for exon 23 and intron 25 of STRC and exon 7 of CATSPER2. Sanger sequencing is used to test the targeted variants in MT-RNR1 (m.1555A>G) and MT-TS1 (m.7445A>G). These regions are amplified by PCR using primers complementary to genomic sequences. DNA sequencing is performed using a commercially available kit (ABI) with di-deoxy terminators. Sequences are analyzed on an automated DNA sequencer (ABI) and compared to reference sequences.
* Sequence analysis only is performed for these genes.
** Copy number analysis only is performed for these genes.
& Targeted variant analysis only is performed for these genes.
CPT Codes
81430
Collection
Collect
Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA and saliva are also acceptable.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
For CHOP Phlebotomy: Samples can be collected throughout the week. Samples collected on weekends or holidays are held in Central Labs and sent to the Genomic Diagnostic Lab the following business day.
For External Clients: Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday, optimally within 24 hours of collection.
Please contact the lab (267-426-1447) with questions regarding non-blood specimens.
Remarks
This analysis includes sequencing and copy number analysis of the genes known to cause nonsyndromic sensorineural hearing loss (NSHL) as well as some syndromic hearing loss that may initially present like NSHL.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Ordering
Clinical Features
Hearing loss is the most prevalent sensory perception deficit disorder in humans, affecting about 1 in 500 newborns, and a genetic etiology is suspected in more than 60% of patients. Hearing loss can be classified as non-syndromic (70%) or syndromic (30%) based on the presence or absence of other associated clinical features.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday-Friday 9:00am - 4:00pm
Reported
42 days
Detection Rate
The Comprehensive AUDIOME panel is intended for the diagnosis of non-syndromic hearing loss (NSHL) and some types of syndromic hearing loss that may initially present as NSHL. This panel includes the examination of sequence variants and copy number variants of the genes listed in the 'Molecular Testing Notes' section and known to cause non-syndromic, syndromic, and both non-syndromic and syndromic hearing loss. Additionally, the testing includes targeted analysis of the MT-RNR1 m.1555A>G (associated with hearing loss following aminoglycoside exposure) and MT-TS1 m.7445A>G (associated with childhood onset sensorineural hearing loss) variants. Isolated CATSPER2 homozygous deletions (without STRC involvement) will not be reported. This analysis may not identify certain types of variants, such as mosaicism, some copy number variants, structural variants, repeat expansions or other long segments of repetitive DNA sequences, some novel variants in the non-coding regions that could affect gene expression (apart from splice site variants) unless specified above. In addition, technically difficult regions (including those that are GC-rich or have high homology) might not be sequenced by this test. The detection limit is 20% for heteroplasmic MT-RNR1 m.1555A>C and MT-TS1 m.7445 A>C variants. A negative result does not exclude the possibility that a proband harbors a pathogenic variant that was undetectable by this test due to the technical limitations. The analysis was dependent on current scientific knowledge of genetic disease at the time of the analysis. Clinical implications of some variants may be uncertain or unknown at the time of this report and may change over time. Interpretations are made with the assumption that any clinical information and family relationships provided to the laboratory are accurate. Please note, this analysis is not designed to report risk alleles for multi-factorial/complex disease or genetic variants implicated in complex disease via genome wide association studies.
Utility
The clinical utility of the assay is to support a clinical diagnosis of hearing loss related phenotypes, facilitate genetic counseling, and assess the risk to first-degree relatives as well as other at-risk family members.
Synonyms
Comprehensive AUDIOME, hearing loss panel, deafness
Genomic DNA is extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing is performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis are based on the GRCh38 reference sequence. Sequencing data is processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants. Long range polymerase chain reaction (LR-PCR) for STRC is performed followed by next generation sequencing. Copy number variants in the STRC (NM_153700.2) and CATSPER2 (NM_172095.4) loci are determined by droplet digital PCR (ddPCR) assays for exon 23 and intron 25 of STRC and exon 7 of CATSPER2. Sanger sequencing is used to test the targeted variants in MT-RNR1 (m.1555A>G) and MT-TS1 (m.7445A>G). These regions are amplified by PCR using primers complementary to genomic sequences. DNA sequencing is performed using a commercially available kit (ABI) with di-deoxy terminators. Sequences are analyzed on an automated DNA sequencer (ABI) and compared to reference sequences.
* Sequence analysis only is performed for these genes.
** Copy number analysis only is performed for these genes.
& Targeted variant analysis only is performed for these genes.
