title: Investigation of Notch3 as a candidate gene for bipolar disorder using brain hyperintensities as an endophenotype.
abstract: The purpose of the study was to consider MRI hyperintensities as a potential endophenotype for bipolar disorder (BPD) and to investigate Notch3 (CADASIL) as a candidate gene for BPD. MRI scans were performed on 21 members of a family with a high incidence of BPD. Two-point and multipoint linkage analyses were performed and two exons of Notch3 were investigated with SSCP. Fifteen of 21 family members had MRI hyperintensities, including all bipolar patients and six family members with no affective illness. Two-point linkage analysis yielded negative results for all models. Multipoint linkage analysis yielded negative results except for Model 1a, in which a maximal LOD score was -1.24. A mutation screen of Exons 3 and 4 was negative. Notch3 does not appear to be a candidate gene for BPD in this family.
authors.affiliation: Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, USA. eileen.ahearn@med.va.gov
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Ahearn
authors.forename: Marcy C
authors.initials: MC
authors.lastname: Speer
authors.forename: Y T
authors.initials: YT
authors.lastname: Chen
authors.forename: David C
authors.initials: DC
authors.lastname: Steffens
authors.forename: Frederick
authors.initials: F
authors.lastname: Cassidy
authors.forename: Susan
authors.initials: S
authors.lastname: Van Meter
authors.forename: James M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: Richard H
authors.initials: RH
authors.lastname: Weisler
authors.forename: K Ranga Rama
authors.initials: KR
authors.lastname: Krishnan
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch
chemical_list: C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch