Specimen:

Whole Blood

Collection Medium:

Minimum:

Preferred Minimum:  8 mL whole blood
Absolute Minimum:  4 mL whole blood

Analytic Time:

8 weeks

Reference Range:

None detected

Interpretive Data:

DFNB1
Two different genes cause hearing loss at this locus, which maps to 
chromosome 13q11-q12:GJB2, encoding Connexin 26; and GJB6, encoding 
Connexin 30.

GJB2 (encodes Connexin 26, CX26)
CX26 is a gap junction protein expressed in the supporting cells of the 
cochlea. The gene, GJB2, contains 2 exons, the second of which encodes 
the 226 amino acid protein CX26. Mutations in GJB2 are found in ~50% of 
persons with autosomal recessive nonsyndromic hearing loss. Over 100 
different mutations have been identified.

GJB6 (encodes Connexin 30, CX30)
CX30 is also a gap junction protein. Lerer and colleagues identified a 
deletion upstream of GJB2, which included the first exon of GJB6 in 
2001. Del Castillo and colleagues characterized this deletion as a 
342kb fragment of chromosome 13 that included D13S1830 in addition to a 
portion of GJB6, and so this deletion is commonly known as the 
del(GJB6-D13S1830) mutation. It cosegregates with mutations in GJB2 to 
cause recessively inherited deafness at the DFNB1 locus. A recent 
multicenter study investigating the mutation spectrum in over 1500 deaf 
persons from 16 countries found this mutation to represent 1.67% of 
mutations at the DFNB1 locus (Van Camp, et al. 2005). A second smaller 
deletion, del(GJB6-D13S1854), also causes deafness at the DFNB1 locus.

Sensitivity is greater than 98%.

Comments:

Please print, complete and submit the Deafness Testing Requisition 
from the Molecular Otolaryngology & Renal Research Laboratory, to 
Specimen Control/Mailouts with the specimen and the Epic Requisition.

Methodology:

Over 97% of the identified mutations at the DFNB1 locus occur in exon 2 
of GJB2 (Van Camp, et al 2005). We have adopted a tiered screening 
process focusing first on exon 2 of GJB2 and the two GJB6-containing 
deletions. The finding of two deafness-causing mutations is consistent 
with the diagnosis of hearing loss at the DFNB1 locus. If one only 
mutation is found, mutation screening for the splice site mutation in 
exon 1 of GJB2 (IVS1 + 1 G>A) is completed. If no deafness-causing 
mutations are found, the diagnosis of hearing loss at the DFNB1 locus 
is excluded based on today’s standards. (GJB2 mutation screening is 
performed by amplification of oligonucleotide primers that flank each 
exon followed by bi-directional sequencing. Screening for the 
del(GJB6-D13S1830) and del(GJB6-D13S1854) mutations is completed by PCR 
amplification of oligonucleotide primers flanking and within the 
deletion breakpoints. Products are run on agarose gel and sized to 
determine presence or absence of a deletion.)

CPT Code:

83891, 83894, 83898 (x3), 83903, 83904 (x4), 83912