Molecular Test Listing

Molecular Requisition

PENDRED SYNDROME
DFNB4
ENLARGED VESTIBULAR AQUEDUCT SYNDROME
SLC26A4 gene analysis

Approximately 1 in 1000 young children have a major hearing impairment (threshold >80dB). Significant hearing loss also occurs in about 1 in 25 people under age 45 and 1 in 10 by age 60 (threshold >25dB). Most of the hearing loss is genetic with over 30 autosomal recessive (70-80%), dominant (23-30%) and X-linked (2-3%) forms. In cases of recessive hearing loss a significant proportion (10-15%) may be ascribed to mutations in the SLC26A4 gene; in addition, variable expressivity has led to speculation there may be a significant underestimation of the contribution of Pendred Syndrome to hearing loss. Mutations in the SLC26A4 gene may also be associated with cases of autosomal dominant hearing loss (DFNB4). In the classical format, Pendred Syndrome may be associated with thyroid abnormalities that lead to increase serum thyroglobulin (detected by a perchlorate discharge testing of radiolabeled iodine); however, variable expression may limit this classical association to 10% of Pendred Syndrome cases. In addition, goiter is also very common in individuals with Pendred Syndrome later in life. The SLC26A4 (Solute Carrier Family 26, member 4) gene has been localized to chromosome 7q31. The gene contains a number of hotspots (L236P, T416P, G384E, 1001+1G*A) and the rest of the mutations are distributed throughout the gene.

• To determine whether a hearing defect in a child is hereditary.
• To identify the potential for abnormal thyroid function and risk of goiter.
• To assess the risk of additional children with hearing loss in an affected family.
• Prenatal testing.

• Sequencing the entire coding sequence of the SLC26A4 gene will identify all published and unique familial mutations as well as examine the intron-exon borders.
  
• DNA sequencing of all 20 exons of the SLC26A4 gene detects a mutation in about 90% of the alleles and 2 mutations in 75% of patients with Pendred Syndrome.

• Blood: EDTA (purple top) tubes
  Newborn: minimum 1-2 mL
  Child/Adult: prefer 2 tubes of 3-5mL blood
  
• Prenatal testing: Please contact the laboratory for instructions

TURNAROUND TIME:      4 Weeks

CPT CODES:    

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