Non-Syndromic Sensorineural Hearing Loss

 

Seventy percent of children with genetic hearing loss have the nonsyndromic form, in which deafness is not associated with any other medical issues or birth defects. Most cases of nonsyndromic hearing loss are inherited in an autosomal recessive manner or by mitochondrial inheritance.

Nonsyndromic hearing loss may involve multiple nuclear or mitochondrial genes. Fifty percent of individuals with autosomal recessive nonsyndromic hearing loss have involvement of the GJB2 (connexin 26) and GJB6 (connexin 30) nuclear genes. Mutations in GJB2 and/or GJB6 are associated with mild to profound hearing impairment that is present at birth. Affected individuals will have two mutation in either the GJB2 or GJB6 genes, or one mutation in each gene.

Genetic hearing loss can also be inherited through changes in mitochondrial genes. Mutations in two mitochondrial genes are commonly associated with syndromic hearing loss: MT-RNR1 and MT-TS1. Furthermore, mutations in MT-RNR1 can be associated with a predisposition to the development of profound bilateral hearing loss after exposure to an aminoglycoside antibiotic.

 

REASONS FOR REFERRAL:

  • Confirmation of a clinical diagnosis in children and adults with unexplained hearing loss.
  • Genetic counseling.

 

GENETICS CENTER HEARING LOSS PANEL TESTING METHODS:

  • Comprehensive NSHL Panel (Connexins 26 and 30 with targeted mitochondrial mutation analysis):
    • Targeted Mutation Analysis for GJB2 (Connexin 26): 35delG, 167delT mutations.
    • Targeted Deletion Analysis for GJB6 (Connexin 30): del(GJB6-D13S1830), del(GJB6-D13S1854).
    • Sequence analysis for GJB2 (Connexin 26): Exons 1 and 2
    • Sequence analysis for specific mitochondrial DNA 1555A>G, 7445A>G mutations.
  • Connexin 26 Targeted Mutation Analysis:
    • Targeted Mutation Analysis for GJB2 (Connexin 26): 35delG, 167delT mutations.
  • Connexin 26 Targeted Deletion Analysis:
    • Targeted Deletion Analysis for GJB6 (Connexin 30): del(GJB6-D13S1830), del(GJB6-D13S1854).
  • Connexin 26 Sequence Analysis:
    • Sequence analysis for GJB2 (Connexin 26): Exons 1 and 2.
  • Mitochondrial Hearing Loss Mutations:
    • Sequence analysis for specific mitochondrial 1555A>G, 7445A>G mutations.

 

TURN AROUND TIME:

  • Targeted Mutation Analysis: 8 days
  • Targeted Deletion Analysis: 7 days
  • Sequence Analysis: 7 days

 
SPECIMEN REQUIREMENTS AND SHIPPING/HANDLING:

  • Blood: A single tube with 1-5 mL whole blood in EDTA (lavender top).
  • Saliva: To request a DNA Mouthwash Collection Kit please contact Genetics Center at (714)288-3500.
  • Shipping: Store blood at 4°C until shipment. Ship at ambient temperature in an insulated container via overnight delivery within 96 hours of collection.

 

Send to:

Genetics Center
211 S. Main Street
Suite AA
Orange, CA 92868
Tel: (714)288-3500

 

REQUIRED FORMS:

 

TEST LIMITATIONS:

Targeted Mutation Analysis tests only for the specified mutations. Gene Sequencing Analysis is unable to detect mutations in regions of the gene not examined, which may include promoter regions, introns, and additional exons unless otherwise specified. Sequencing may be unable to detect large deletions and/or insertions and chromosomal rearrangements. It is possible that some patients may carry a rare mutation of this nature not detected by this assay. This assay may detect polymorphisms of unknown clinical significance, which may require further studies.

 

CPT CODES:

  • Connexin 26 (GJB2)
    • CPT’s: 81253, G0452
  • Connexin 26 Sequencing (GJB2)
    • CPT’s: 81252, G0452
  • Connexin 30 (GJB6)
    • CPT’s: 81254, G0452
  • Mitochondrial Hearing Loss Sequencing (MT-RNR1 & MT-TS1)
    • CPT’s: 81404, G0452
  • Hearing Loss Panel
    • CPT’s: 81252, 81254, 81404, G0452x3