A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases.
A recent report has shown that Wolfram syndrome carriers (heterozygotes) are 26-fold more likely to require psychiatric hospitalization compared with non-carriers, and that Wolfram syndrome heterozygotes may constitute approximately 25% of individuals hospitalized with depression and suicide attempts. We analyzed a His611Arg polymorphism of the wolframin gene by the polymerase chain reaction (PCR) and HhaI restriction digestion, in 158 bipolar I and 163 unipolar major affective disorder cases, and 316 controls. Statistical analyses of allele or genotype frequencies do not support a major role for wolframin in affective disorder. HhaI restriction digestion and sequencing of PCR products from four affective disorder cases showed a heterozygous Ala559Thr change. The Ala559Thr variant was not detectable in 382 controls tested. Thus, the rare wolframin 559Thr allele deserves consideration as a risk allele for affective disorder.
Furlong
R A
RA
Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke's Hospital, UK.
Ho
L W
LW
Rubinsztein
J S
JS
Michael
A
A
Walsh
C
C
Paykel
E S
ES
Rubinsztein
D C
DC
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D003062:Codon / Q000235:genetics; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D019964:Mood Disorders / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D014929:Wolfram Syndrome / Q000235:genetics*
D003062:Codon; D008565:Membrane Proteins; C114987:wolframin protein