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A third gene locus for tuberous sclerosis is closely linked to the phenylalanine hydroxylase gene locus

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Summary

Following the observation of a patient suffering from tuberous sclerosis (TSC) with a de novo reciprocal translocation t(3;12)(p26.3;q23.3), we have undertaken a linkage study in 15 TSC families using polymorphic DNA markers neighbouring the chromosome breakpoints. Significant lod scores have been obtained for markers D12S7 (z max=2.34, θ=0.14) and PAH (phenylalanine hydroxylase) (z max=4.34, θ=0.0). In multipoint linkage analysis, the peak lod score was 4.56 at the PAH gene locus. These data suggest the existence of a third gene locus for TSC (TSC3) on chromosome 12q22-24.1. The regions that have been found to be linked to TSC in different families map to the positions of three enzymes, phenylalanine hydroxylase (12q22-24), tyrosinase (11q14-22), and dopamine-beta-hydroxylase (9q34), all of which are involved in the conversion of phenylalanine to catecholamine neurotransmitters or melanin. Disorders of these biochemical pathways might be involved in the pathogenesis of TSC.

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Authors and Affiliations

  1. Institut für Humangenetik, Universität Erlangen-Nürnberg, Schwabachanlage 10, W-8520, Erlangen, Germany

    R. Fahsold & H. -D. Rott

  2. Institut für Klinische Genetik, Medizinische Akademie “Karl-Gustav Karus”, O-8019, Dresden, Germany

    P. Lorenz

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  1. R. Fahsold
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  2. H. -D. Rott
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  3. P. Lorenz
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Fahsold, R., Rott, H.D. & Lorenz, P. A third gene locus for tuberous sclerosis is closely linked to the phenylalanine hydroxylase gene locus. Hum Genet 88, 85–90 (1991). https://doi.org/10.1007/BF00204934

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  • DOI: https://doi.org/10.1007/BF00204934

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