Abstract
Identifying genetic loci at which mutations predispose individuals to common psychiatric
illnesses will have major impact on the diagnosis and treatment of mental illness.
The available evidence indicates that mutations at the Wolfram syndrome locus contribute
substantially to the prevalence of psychiatric illness in the general population.
Patients with mutations at this locus on both parental chromosomes, called Wolfram
syndrome homozygotes, have a distinctive and rare autosomal recessive syndrome characterized
by juvenile onset diabetes mellitus and bilateral progressive optic atrophy. Diverse
and serious psychiatric manifestations frequently have been observed in Wolfram syndrome
patients; however, the population burden of mental illness attributable to mutations
at this locus is almost entirely from individuals who carry a single mutation, called
Wolfram syndrome heterozygotes, who have no distinguishing physical characteristics
but constitute approximately 1% of the population.
Molecular genotyping of blood relatives of Wolfram syndrome patients has shown that
Wolfram syndrome heterozygotes are 26-fold more likely than noncarriers to have a
psychiatric hospitalization. Severe depression was the predominant finding in the
test group studied. The prediction that approximately 25% of all patients hospitalized
for depression are Wolfram syndrome heterozygotes now can be tested by mutation screening
of hospitalized patients from the general population. Many other behavioral and cognitive
difficulties also have been observed in Wolfram syndrome families. For each specific
psychiatric abnormality, a “test group” of blood relatives within Wolfram syndrome
families with that abnormality can be formed. By comparing the number of Wolfram syndrome
heterozygotes found in each test group by molecular genotyping with the number expected
under the null hypothesis, the index-test method can determine which clinical phenotypes
result from mutations at the Wolfram syndrome locus. This method can be utilized to
identify other loci at which mutations predispose individuals to psychiatric illnesses.
Keywords
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Article info
Publication history
Accepted:
January 6,
2000
Received in revised form:
December 23,
1999
Received:
September 27,
1999
Identification
Copyright
© 2000 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
