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@email.chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled blood 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.
Volume Required
Blood – 3-5mL of blood in an EDTA (purple top) tube.
DNA –5-10ug of DNA with a minimum concentration of 50ng/uL.
Minimum Required
3mL
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. Biallelic pathogenic variants in the STRC gene cause autosomal recessive hearing loss 16 [OMIM #603720], which is typically characterized by congenital to post-lingual onset, mild to moderate, non-syndromic, bilateral sensorineural hearing loss. The most common pathogenic STRC alterations are whole or partial deletions that often extend into the CATSPER2 gene, resulting in autosomal recessive deafness-infertility syndrome, a contiguous gene deletion syndrome characterized by early-onset deafness in both males and females and infertility in males [Villamar 1999, PMID: 10090914; Mandelker 2014, PMID: 25157971; Vona 2015, PMID: 26011646; Francey 2012, PMID: 22147502].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday – Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
Although the specific population frequency varies depending on ethnicity and type of hearing loss, biallelic pathogenic STRC alterations are known to be a major cause of hearing loss, estimated to account for approximately 16 to 25% of genetic hearing loss (up to 6% of all hearing loss), and to be the most common cause of mild-to-moderate autosomal recessive hearing loss. The vast majority of pathogenic STRC alterations are large deletions encompassing all or part of STRC, while pathogenic sequence variants contribute to a smaller portion of cases [Sloan-Heggen 2016, PMID: 26969326; Vona 2015, PMID: 26011646; Amr 2018, PMID: 29339441; Francey 2012, PMID: 22147502].
Utility
The clinical utility of the assay is to support a clinical diagnosis of hearing loss, facilitate genetic counseling, and assess the risk to other first-degree relatives, as well as at-risk family members.
This test includes sequence and deletion/duplication analysis of the STRC gene. Analysis of STRC can be challenging due to the existence of a highly homologous pseudogene. Therefore, STRC sequence analysis is performed by long-range PCR and next generation sequencing, and STRC copy number variation (CNV) detection is performed by digital droplet PCR (ddPCR), which can detect the common deletions involving STRC, including those containing CATSPER2. Isolated CATSPER2 deletions (without STRC involvement) will not be reported. Variants that are classified as benign or likely benign are typically not confirmed or reported. Variants of uncertain significance may warrant further studies in the patient and/or other family members.
Molecular Testing Notes
STRC analysis (sequencing and deletion/duplication analysis) is also available as a part of the Audiome test.
CPT Codes
81479
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@email.chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled blood 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.
Volume Required
Blood – 3-5mL of blood in an EDTA (purple top) tube.
DNA –5-10ug of DNA with a minimum concentration of 50ng/uL.
Minimum Required
3mL
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. Biallelic pathogenic variants in the STRC gene cause autosomal recessive hearing loss 16 [OMIM #603720], which is typically characterized by congenital to post-lingual onset, mild to moderate, non-syndromic, bilateral sensorineural hearing loss. The most common pathogenic STRC alterations are whole or partial deletions that often extend into the CATSPER2 gene, resulting in autosomal recessive deafness-infertility syndrome, a contiguous gene deletion syndrome characterized by early-onset deafness in both males and females and infertility in males [Villamar 1999, PMID: 10090914; Mandelker 2014, PMID: 25157971; Vona 2015, PMID: 26011646; Francey 2012, PMID: 22147502].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday – Friday, 9:00am to 4:00pm
Reported
28 days
Detection Rate
Although the specific population frequency varies depending on ethnicity and type of hearing loss, biallelic pathogenic STRC alterations are known to be a major cause of hearing loss, estimated to account for approximately 16 to 25% of genetic hearing loss (up to 6% of all hearing loss), and to be the most common cause of mild-to-moderate autosomal recessive hearing loss. The vast majority of pathogenic STRC alterations are large deletions encompassing all or part of STRC, while pathogenic sequence variants contribute to a smaller portion of cases [Sloan-Heggen 2016, PMID: 26969326; Vona 2015, PMID: 26011646; Amr 2018, PMID: 29339441; Francey 2012, PMID: 22147502].
Utility
The clinical utility of the assay is to support a clinical diagnosis of hearing loss, facilitate genetic counseling, and assess the risk to other first-degree relatives, as well as at-risk family members.
This test includes sequence and deletion/duplication analysis of the STRC gene. Analysis of STRC can be challenging due to the existence of a highly homologous pseudogene. Therefore, STRC sequence analysis is performed by long-range PCR and next generation sequencing, and STRC copy number variation (CNV) detection is performed by digital droplet PCR (ddPCR), which can detect the common deletions involving STRC, including those containing CATSPER2. Isolated CATSPER2 deletions (without STRC involvement) will not be reported. Variants that are classified as benign or likely benign are typically not confirmed or reported. Variants of uncertain significance may warrant further studies in the patient and/or other family members.
Molecular Testing Notes
STRC analysis (sequencing and deletion/duplication analysis) is also available as a part of the Audiome test.
