GJB2/GJB6 (Connexin 26,30) Gene Analysis
Label Mnemonic: GJBMORL
Epic Lab Code: LAB7848
Downtime Form: A-1a Miscellaneous Request
Commercial Mail-out Laboratory
5231 RCP
356-8593
Specimen(s):
Whole Blood
Specimen Instructions:
Please include the following information: • Patient identifiers (full name, date of birth, sex and medical record number) • Patient address, necessary for receipt and/or reporting results • Pertinent history and clinical findings • Date of collection & Sample type • Ordering physician
Collection Medium:
and
Pink top tube 6 mL (K2-EDTA) Pink top tube 6 mL (K2-EDTA)
Minimum:
Preferred Minimum: 8 mL whole blood
Absolute Minimum: 4 mL whole blood
Turn Around 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 Hearing Loss Testing Requisition Form 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:
GJB2 - 81252
GJB6 - 81254