¹Department of Psychiatry, The Institute for the Genetic Analysis of Common Diseases, New York Medical College, 4 Skyline Drive, Hawthorne, New York 10532, USA

²Laboratory of Genetic Disease Research, Gene Mapping Unit, National Human Genome Research Institute, National Institutes of Health, Bldg 49, Rm 4A66, Bethesda, MD 20892, USA

³Department of Pediatrics, The Institute for the Genetic Analysis of Common Diseases, New York Medical College, 4 Skyline Drive, Hawthorne, New York 10532, USA

Identification of specific genes that predispose to psychiatric illness will lead to more precise psychiatric diagnosis and more effective treatment. Heterozygous carriers of genes for many autosomal recessive syndromes may be 1% or more of the general population. Thus, if mutations at a specific locus produce psychiatric manifestations in homozygous affected individuals, it is important to determine whether mutations at such a locus also predispose heterozygous carriers to psychiatric disorders. The hypothesis that heterozygous carriers of the gene for the Wolfram syndrome (WS) are predisposed to psychiatric illness was supported previously by the finding of an excess of psychiatric hospitalizations and suicides in WS blood relatives compared to spouse controls.¹ This hypothesis has now been tested further by comparing the number of psychiatrically hospitalized blood relatives with the specific marker haplotype associated with the Wolfram syndrome gene in their families to the number expected under the null hypothesis, calculated from Mendelian inheritance principles and the estimated haplotype frequency.² The proportion of psychiatrically hospitalized relatives who were WS carriers (10/11) was much higher than expected (3.1/11), leading to the provisional estimate that WS gene carriers are 26-fold more likely to require psychiatric hospitalization than non-carriers.

Wolfram syndrome; heterozygotes; psychiatric illness