title: Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q.
abstract: Idiopathic basal ganglia calcification (IBGC) is characterised by radiological, neurological, cognitive and psychiatric abnormalities. The associations between these abnormal phenotypes and abnormal genes remain unclear despite the recent mapping to chromosome 14q of a susceptibility locus for IBGC ( IBGC1). We identified two siblings, from a large multigenerational pedigree, who had both been diagnosed with radiological IBGC, dementia, bipolar affective disorder and Parkinsonism. We assessed (1) other family members to determine whether these four phenotypes were co-segregating as symptoms of IBGC, and (2) possible IBGC linkage to the IBGC1 locus on chromosome 14q or to any known or potential dementia genes. Nine second-generation and 21 third-generation members received radiological, neurological, neuropsychological and psychiatric assessments. We genotyped all family members for microsatellite markers at the IBGC1 locus and polymorphisms of the ApoE, VLDL, alpha1-ACT, BChE-K, APP, PS1, PS2 and tau genes and tested these for linkage to IBGC, dementia and bipolar disorder. Of the ten family members with radiological intracranial calcification, all except the two index cases were normal. There was no significant association between IBGC status and severe cognitive impairment or dementia ( P=0.335) or bipolar affective disorder or Parkinsonism ( P=1.0). Linkage to the IBGC1 locus was excluded. Of the eight dementia gene markers tested, the only positive LOD score was for the ApoE epsilon4 polymorphism and dementia/severe cognitive impairment. We have identified a form of IBGC in which calcification is inherited independently of neurological, cognitive and psychiatric symptoms. This may represent a second locus for this disorder.
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, Australia, h.brodaty@unsw.edu.au
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.forename: Philip
authors.initials: P
authors.lastname: Mitchell
authors.forename: Georgina
authors.initials: G
authors.lastname: Luscombe
authors.forename: John J
authors.initials: JJ
authors.lastname: Kwok
authors.forename: Renee F
authors.initials: RF
authors.lastname: Badenhop
authors.forename: Rod
authors.initials: R
authors.lastname: McKenzie
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D001480:Basal Ganglia Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000523:psychology; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000523:psychology; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D009679:Nuclear Family; D010375:Pedigree; D011581:Psychological Tests; D014057:Tomography, X-Ray Computed
chemical_list: D005819:Genetic Markers