Abstract
Hereditary non-syndromic deafness has been associated with a point mutation in the mitochondrial 12S rRNA gene. We present data from deaf individuals in 12 nuclear families originating from a small village in Zaire. The patients have a sudden-onset and profound, bilateral sensorineural deafness with a highly variable age of onset. Inheritance is compatible with a mitochondrial DNA defect. Sequencing of the mitochondrial 12S rRNA gene revealed the presence of a homoplasmic 1555 A to G mutation in the patients and their normal siblings. The mutation is invariably associated with a T to C transition at 1420 in the same gene. Additional (mitochondrial or autosomal) genetic defect(s) or an environmental factor must be implicated in the expression of the defect. In Epstein-Barr-virus-transformed lymphocytes harbouring the normal or mutant mitochondrial DNA, no differential effect of aminoglycosides on protein translation was observed.
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Acknowledgements
We wish to thank M. Willems, G. Deferme and L. Mekers for establishing EBV-lymphocytes and skin fibroblast cultures, and R. Decorte and E. Jehaes for assistance in sequencing the D-loop variable regions. We are indebted to Prof. R. De Wachter for the alignments of 12S rRNA genes of about 50 species, and to Dr. M. Jorissen for commenting on the audiograms. We thank Dr. E. Legius and Prof. P. Marynen for critically reading the manuscript. Dr. L. Standaert from the Spermalie Instituut in Brugge collected the samples from deaf children for us. The help of many collaborators in Kinshasa and in Kai Singini, and the contribution of the families are gratefully acknowledged. The families have expressed a great wish towards the understanding and the cure of this mysterious disease. G.M. is a ‘Post-doctoraal Onderzoeker’ and S.C. an ‘Aspirant’ of the National Foundation for Scientific Research, Belgium. This investigation was supported by grant ‘S2/5-ID. E103’ of the Fonds voor Geneeskundig Wetenschappelijk Onderzoek, Belgium and by the Inter-University Network for Fundamental Research sponsored by the Belgian Government (1991–1996).
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Matthijs, G., Claes, S., Longo-Mbenza, B. et al. Non-Syndromic Deafness Associated with a Mutation and a Polymorphism in the Mitochondrial 12S Ribosomal RNA Gene in a Large Zairean Pedigree. Eur J Hum Genet 4, 46–51 (1996). https://doi.org/10.1159/000472169
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DOI: https://doi.org/10.1159/000472169
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