caa a22 4500 606182691 CHVBK 20210128100817.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00405-014-3223-z doi (NATIONALLICENCE)springer-10.1007/s00405-014-3223-z The promoter mutation c.−259C>T (−3438C>T) is not a common cause of non-syndromic hearing impairment in Austria [Elektronische Daten] [Martin Koenighofer, Trevor Lucas, Thomas Parzefall, Reinhard Ramsebner, Christian Schoefer, Klemens Frei] 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. Springer-Verlag Berlin Heidelberg, 2014 Promoter regions nationallicence Genetics nationallicence Hearing loss, sensorineural nationallicence Neonatal screening nationallicence Connexin 26 nationallicence Regulatory sequences, nucleic acid nationallicence Koenighofer Martin Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria aut Lucas Trevor Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria aut Parzefall Thomas Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria aut Ramsebner Reinhard Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria aut Schoefer Christian Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria aut Frei Klemens Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria aut European Archives of Oto-Rhino-Laryngology Springer Berlin Heidelberg 272/1(2015-01-01), 229-232 0937-4477 272:1<229 2015 272 405 https://doi.org/10.1007/s00405-014-3223-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00405-014-3223-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Koenighofer Martin Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Lucas Trevor Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria aut NATIONALLICENCE 700 1- Parzefall Thomas Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Ramsebner Reinhard Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 700 1- Schoefer Christian Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria aut NATIONALLICENCE 700 1- Frei Klemens Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria aut NATIONALLICENCE 773 0- European Archives of Oto-Rhino-Laryngology Springer Berlin Heidelberg 272/1(2015-01-01), 229-232 0937-4477 272:1<229 2015 272 405