title: The promoter mutation c.-259C>T (-3438C>T) is not a common cause of non-syndromic hearing impairment in Austria.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Medical University of Vienna, AKH 8J, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Koenighofer
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
authors.forename: Thomas
authors.initials: T
authors.lastname: Parzefall
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ramsebner
authors.forename: Christian
authors.initials: C
authors.lastname: Schoefer
authors.forename: Klemens
authors.initials: K
authors.lastname: Frei
mesh_terms: D001317:Austria / Q000453:epidemiology; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011401:Promoter Regions, Genetic
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D004247:DNA
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