The promoter mutation c.−259C>T (−3438C>T) is not a common cause of non-syndromic hearing impairment in Austria
The objective of this study was to investigate the relevance of routine assessment of c.−259C>T in the Austrian newborn screening program. Homozygous and compound heterozygous mutations in the coding region of the human gene encoding gap junction protein GJB2 (Connexin 26) cause up to 50 % of neo...
Gespeichert in:
Veröffentlicht in: | European archives of oto-rhino-laryngology 2015-01, Vol.272 (1), p.229-232 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | The objective of this study was to investigate the relevance of routine assessment of c.−259C>T in the Austrian newborn screening program. Homozygous and compound heterozygous mutations in the coding region of the human gene encoding gap junction protein GJB2 (Connexin 26) cause up to 50 % of neonatal autosomal recessive non-syndromic hearing impairment identified in Caucasian newborn screening programs. More recently, a null mutation in the GC box of the
GJB2
basal promoter c.−259C>T has been described which causes hearing impairment by completely suppressing
GJB2
promoter activity. We determined the occurrence of c.−259C>T in cases of non-syndromic hearing impairment lacking known pathogenic alterations in
GJB2
(
n
= 43), a non-syndromic hearing impaired patient group (
n
= 15) bearing the heterozygous
GJB2
mutations c.35delG, c.[79G>A];[341A>G] (p. [V27I];[E114G]), c.109G>A (p.V37I), c.154G>C (p.V52L), c.262G>T (p.A88S), c.269T>C (p.L90P) and c.551G>C (p.R184P) and in a normal hearing group lacking alterations in
GJB2
(
n
= 50). In the analyzed groups, no occurrence of c.−259C>T was found. The c.−259C>T mutation, previously described as −3438C>T, is not a common cause of non-syndromic hearing impairment alone or together with heterozygous pathogenic
GJB2
mutations that are statistically overrepresented in non-syndromic hearing impaired patient groups. Screening of newborns for c.−259C>T is therefore unlikely to be commonly found in Austrian NSHI patients but could make a significant contribution to non-syndromic hearing impairment in other populations. |
---|---|
ISSN: | 0937-4477 1434-4726 |
DOI: | 10.1007/s00405-014-3223-z |