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The report by Matos et al1 brings up an issue of an excessive frequency of patients with hearing impairment (HI) in whom only monoallelic GJB2 mutations are identified by commonly used testing strategies. Interestingly, Matos et al suggest that these patients could harbour mutations in promoter of GJB2 which therefore should be included in the routine screening.1 This conclusion was supported by a novel sequence variant (−3438T→C) affecting GJB2 promoter function and found in a Portuguese patient in trans with a coding region mutation.1
The relatively high frequency of genotypes with monoallelic GJB2 mutations, such as the 35delG mutation, among the patients has indeed been noted previously2 3 although the exact size of this effect in relation to the generally high frequency of 35delG in Caucasians (carrier rates reaching 4%)4 has not been estimated. Although screening of promoter regions is clearly an attractive option in patients with monoallelic GJB2 defects, before it can be included in routine testing it should be shown that the −3438T→C or similar alteration(s) do indeed occur with an appreciable frequency.
Given the report of Matos et al,1 we were interested to find out: (1) whether there is an excess of monoallelic GJB2 mutations among patients with HI from our centre and if so, what is its magnitude, and (2) what is the frequency of GJB2 promoter mutations such as −3438T→C among such patients. Owing to the high frequency …