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Uniparental disomy of chromosome 13q causing homozygosity for the 35delG mutation in the gene encoding connexin26 (GJB2) results in prelingual hearing impairment in two unrelated Spanish patients
  1. A Álvarez1,
  2. I del Castillo1,
  3. A Pera1,
  4. M Villamar1,
  5. M A Moreno-Pelayo1,
  6. T Rivera2,
  7. J Solanellas3,
  8. F Moreno1
  1. 1Unidad de Genética Molecular, Hospital Ramón y Cajal, Madrid, Spain
  2. 2Servicio de ORL, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
  3. 3Servicio de ORL, Hospital Universitario Nuestra Señora de Valme, Sevilla, Spain
  1. Correspondence to:
 Dr F Moreno, Unidad de Genética Molecular, Hospital Ramón y Cajal, Carretera de Colmenar, Km 9, 28034 Madrid, Spain; 

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Inherited hearing impairment is a highly heterogeneous group of disorders with an overall incidence of about 1 in 2000 newborns.1 In approximately 70% of cases, the auditory impairment is not associated with other clinical features, that is, it is non-syndromic. The most frequent condition is a severe or profound hearing loss of prelingual onset, which is inherited mainly as an autosomal recessive trait.1 To date, 31 different DFNB loci for autosomal recessive non-syndromic hearing loss have been reported, and 16 genes have been identified.2 Among these loci, DFNB1 in 13q12 stands out because of its complexity and clinical relevance. It contains the gene GJB2, which encodes connexin26, a component of intercellular gap junctions. Mutations in the GJB2 gene are responsible for up to 50% of all cases of autosomal recessive hearing impairment in most of the populations tested so far, with a frequent mutation (35delG) accounting for up to 86% of the GJB2 mutant alleles in white populations.3,4 However, not all the DFNB1 mutations affect the GJB2 gene. Recently, several research teams found a deletion in the 13q12 region which is frequently inherited in double heterozygosity with mutant GJB2 alleles in affected subjects,5–7 but it was also found in homozygosity.6,7 Molecular characterisation of this deletion, termed del(GJB6-D13S1830), showed that it encompasses 342 kb and it does not affect the GJB2 gene, but it truncates the gene encoding connexin30 (GJB6), another gap junction protein expressed in the inner ear.6 The existence of this deletion was first suspected by the finding of inconsistencies in the segregation of genetic markers distal to GJB2.

Key points

  • Mutations in the gene encoding the gap junction protein connexin26 (DFNB1 locus on 13q12) are responsible for up to 50% of all cases of …

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