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.
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 is designed to detect the main genetic changes associated with DFNB1-related hearing loss.
Volume Required
3 ml per tube
Minimum Required
3 ml
Phlebotomy Draw
Yes
Clinical Features
Biallelic pathogenic variants in the DFNB1 locus (on chromosome 13q12) cause a form of autosomal recessive nonsyndromic hearing loss and deafness (DFNB1), which is characterized by congenital non-progressive mild-to-profound sensorineural hearing impairment. Homozygous or compound heterozygous GJB2 pathogenic variants have been detected in ~99% of patients. The remaining 1% of patients with hearing loss due to mutations at the DFNB1 locus can be compound heterozygous for one GJB2 pathogenic variant and one deletion involving sequences upstream of GJB2 and a portion of GJB6. Although uncommon, some heterozygous variants in the GJB2 gene can cause autosomal dominant syndromic hearing loss with associated skin findings. [GeneReviews 2016, PMID: 20301449; Alford 2014, PMID: 24651602].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday-Friday 9:00am - 4:00pm
Methodology
Sequence analysis of the entire coding, promoter, and 3' UTR regions of the GJB2 gene and targeted testing for the ΔGJB6-D13S1830 variant in the DFNB1 locus.
Reported
21 days
Detection Rate
Testing DFNB1 locus is expected to result in a molecular diagnosis in 15-40% of hearing loss cases in a variety of populations or in up to 50% of all autosomal recessive nonsyndromic hearing loss.
Sanger sequencing of the entire coding, promoter, and 3' UTR regions of the GJB2 gene is expected to identify the majority of single nucleotide variants. Copy number variants other than the common deletion ΔGJB6-D13S1830 variant in DFNB1 locus will not be targeted for testing.
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
DFNB1, GJB2, GJB6, hearing loss, deafness
LIS Mnemonic
DFNBS
Available STAT
No
CPT Codes
81252, 81254
Collection
Collect
2 EDTA (lavender top tubes) whole blood.
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.
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 is designed to detect the main genetic changes associated with DFNB1-related hearing loss.
Volume Required
3 ml per tube
Minimum Required
3 ml
Phlebotomy Draw
Yes
Ordering
Clinical Features
Biallelic pathogenic variants in the DFNB1 locus (on chromosome 13q12) cause a form of autosomal recessive nonsyndromic hearing loss and deafness (DFNB1), which is characterized by congenital non-progressive mild-to-profound sensorineural hearing impairment. Homozygous or compound heterozygous GJB2 pathogenic variants have been detected in ~99% of patients. The remaining 1% of patients with hearing loss due to mutations at the DFNB1 locus can be compound heterozygous for one GJB2 pathogenic variant and one deletion involving sequences upstream of GJB2 and a portion of GJB6. Although uncommon, some heterozygous variants in the GJB2 gene can cause autosomal dominant syndromic hearing loss with associated skin findings. [GeneReviews 2016, PMID: 20301449; Alford 2014, PMID: 24651602].
Performing Lab
Division of Genomic Diagnostics
Performed
Monday-Friday 9:00am - 4:00pm
Methodology
Sequence analysis of the entire coding, promoter, and 3' UTR regions of the GJB2 gene and targeted testing for the ΔGJB6-D13S1830 variant in the DFNB1 locus.
Reported
21 days
Detection Rate
Testing DFNB1 locus is expected to result in a molecular diagnosis in 15-40% of hearing loss cases in a variety of populations or in up to 50% of all autosomal recessive nonsyndromic hearing loss.
Sanger sequencing of the entire coding, promoter, and 3' UTR regions of the GJB2 gene is expected to identify the majority of single nucleotide variants. Copy number variants other than the common deletion ΔGJB6-D13S1830 variant in DFNB1 locus will not be targeted for testing.
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.
