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A second large family with catatonic schizophrenia supports the region distally of CHRNA7 on chromosome 15q14–15

Molecular Psychiatry volume 8, pages 259–260 (2003)Cite this article

We agree with Leonard and Freedman1 that the gene encoding the nicotinic acetylcholine receptor α7 subunit (CHRNA7) may play a role in schizophrenia, and that more than one gene from the chromosome 15q14 region could be involved in the pathogenesis of different forms of schizophrenia. However, our set of genetic data derived from large families does not provide evidence that CHRNA7 causes hereditary catatonic schizophrenia (SCZD10, periodic catatonia, OMIM 605419). Leonard and Freedman present a pedigree depicting a proband with three offsprings, all four affected with schizophrenia. These patients share polymorphic marker alleles centromeric of CHRNA7, thus excluding the genes distally of CHRNA7 as candidates, whereas a schizophrenia-related gene located telomeric of CHRNA7 has recently been suggested by our group.2 Leonard and Freedman conclude that their family is more informative than our three-generation family with seven affected members, and their criticism is mainly based on the observation that affected members of the informative branch share the same 15q13–22 haplotype from the other parent (proband 0731), who has married into our extended family. Therefore, this individual could also be considered as a theoretical source for a disease mutation in the branch. However, no cases of psychiatric disorders have been reported for any members of the family of proband 0731.3,4

Although a second vulnerability gene may be localized in this region, cosegregation of chromosome 15 related markers and schizophrenia observed in the NIH family reported by Leonard and Freedman could also be due to chance. Sharing of common markers of any chromosomal regions divided by only three meioses is expectable for one out of four of all chromosomal loci in such a small family, resulting in a lod score of 0.6. In other words, one may expect cosegregation of markers of any chromosomal locus with a given disease coincidentally in one out of four families of this size.

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References

  1. Leonard S, Freedman R . Mol Psychiatry 2003; 8: 145–147.

  2. Meyer J et al. Mol Psychiatry 2002; 7: 220–223.

  3. Stöber G et al. Am J Hum Genet 2000; 67: 1201–1207.

  4. Stöber G et al. Eur Arch Psychiatry Clin Neurosci 2001 (Suppl 1): I/25–I/30.

  5. Stöber G et al. Hum Genet 2002; 111: 323–330.

  6. Meyer J et al. Am J Med Genet 2002; 114: 860 (Abstract).

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany

    J Meyer & K P Lesch

  2. Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Sigmund-Freud-Str. 25, Bonn, D-53105, Germany

    F Rüschendorf

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  1. J Meyer
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  2. F Rüschendorf
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  3. K P Lesch
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Correspondence to J Meyer.

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Meyer, J., Rüschendorf, F. & Lesch, K. A second large family with catatonic schizophrenia supports the region distally of CHRNA7 on chromosome 15q14–15. Mol Psychiatry 8, 259–260 (2003). https://doi.org/10.1038/sj.mp.4001222

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