The role of alternative GJB2 transcription in screening for neonatal sensorineural deafness in Austria.
CONCLUSIONS
Alterations within a novel putative Exon 1a within the gap junction beta 2 (GJB2) gene may play a role in the development of genetic hearing impairment in Austria.


OBJECTIVE
Mutations in the GJB2 gene are the most common cause of hereditary sensorineural deafness. Genome-wide screening for alternative transcriptional start sites in the human genome has revealed the presence of an additional GJB2 exon (E1a). This study tested the hypothesis of whether alternative GJB2 transcription involving E1a may play a role in the development of congenital sensorineural deafness in Austria.


METHODS
GJB2 E1a and flanking regions were sequenced in randomized normal hearing control subjects and three different patient groups with non-syndromic hearing impairment (NSHI), and bioinformatic analysis was performed. Statistical analysis of disease association was carried out using the Cochran-Armitage test for trend.


RESULTS
A single change 2410 bp proximal to the translational start site (c.-2410T > C, rs7994748, NM_004004.5:c.-23 + 792T > C) was found to be significantly associated with the common c.35delG GJB2 mutation (p = .009). c.35delG in combination with c.-2410CC occurred at a 6.9-fold increased frequency compared to the control group. Additionally, one patient with idiopathic congenital hearing loss was found to be homozygous c.-2410CC.
a Department of Otorhinolaryngology , Medical University of Vienna , Austria.
Thomas
T
Parzefall
b Department for Cell- and Developmental Biology , Medical University of Vienna , Austria.
Trevor
T
Lucas
a Department of Otorhinolaryngology , Medical University of Vienna , Austria.
Martin
M
Koenighofer
a Department of Otorhinolaryngology , Medical University of Vienna , Austria.
Reinhard
R
Ramsebner
b Department for Cell- and Developmental Biology , Medical University of Vienna , Austria.
Alexandra
A
Frohne
b Department for Cell- and Developmental Biology , Medical University of Vienna , Austria.
Shelly
S
Czeiger
a Department of Otorhinolaryngology , Medical University of Vienna , Austria.
Wolf-Dieter
WD
Baumgartner
b Department for Cell- and Developmental Biology , Medical University of Vienna , Austria.
Christian
C
Schoefer
a Department of Otorhinolaryngology , Medical University of Vienna , Austria.
Wolfgang
W
Gstoettner
a Department of Otorhinolaryngology , Medical University of Vienna , Austria.
Klemens
K
Frei
D017398:Alternative Splicing; D001317:Austria; D001483:Base Sequence; D016022:Case-Control Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008403:Mass Screening; D011110:Polymorphism, Genetic
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
Alternative transcription; DFNB1; GJB2; connexin 26; hereditary deafness; non-syndromic hearing impairment