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Recurrent mutations in the deafness geneGJB2 (connexin 26) in British Asian families
  1. Sarah Rickarda,f,
  2. David P Kelsellb,
  3. Tony Sirimanac,
  4. Kaukab Rajputd,
  5. Breege MacArdlee,
  6. Maria Bitner-Glindziczf
  1. aThe North Thames (East) Regional Clinical Molecular Genetics Laboratory, Level 5, Camelia Botnar Laboratories, Great Ormond Street, London WC1N 3JH, UK, bCentre for Cutaneous Research, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, 2 Newark Street, London E1 2AT, UK, cDepartment of Audiological Medicine, Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK, dDepartment of Cochlear Implant, Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK, eDepartment of Audiological Medicine, Royal National Throat Nose and Ear Hospital, Grays Inn Road, London WC1X 8DA, UK, fUnit of Clinical and Molecular Genetics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
  1. Dr Bitner-Glindzicz, mbitnerg{at}

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Editor—Mutations inGJB2, the connexin 26 (Cx26) gene, are thought to account for over 50% of autosomal recessive, non-syndromic, congenital deafness, the most common form of genetic deafness1 2 and 10-30% of sporadic cases.2 3 Over 50 recessive mutations in theGJB2 gene have been reported since it was originally described4 (the connexin 26(GJB2) deafness homepage at The most common mutation is a deletion of a guanosine nucleotide at position 30-35 (35delG), accounting for approximately 30-63% of mutations in white populations with a carrier frequency of 1:31 in Mediterranean populations.1 2 However, the 35delG mutation is present at a lower prevalence in different ethnic groups,5-8 with other mutations occurring at a higher prevalence, such as 167delT in the Jewish population.9-12 Both the high carrier frequency of GJB2 mutations and the prevalence of non-35delG mutations in non-white populations implies that mutations other than 35delG may be more common in non-white ethnic minorities who have settled in the UK, particularly those in which consanguinity is prevalent.

In order to examine strategies suitable for sensitive, medium throughput mutation detection in GJB2, we used denaturing high performance liquid chromatography (DHPLC) to screen for mutations in a cohort of 51 multi-ethnic patients with non-syndromic deafness who presented at our centre for genetic counselling. We found that DHPLC detected all the control mutations in the sample and that no mutations were identified by sequencing that were not detected by DHPLC. Three mutations, W24X, W77X, and Q124X, found in Indian, Pakistani, and Bangladeshi families in this study, have been previously observed in families from the Indian subcontinent, suggesting that they may be common mutations in these ethnic groups.

Methods and results

Fifty one subjects with non-syndromic hearing loss were ascertained through genetic counselling and audiological medicine clinics at Great …

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