Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease).
Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative syndrome that is associated with a variety of movement disorders and neurobehavioral and cognitive manifestations. Despite numerous clinical, pathological, and biochemical investigations, its etiology remains unknown. We have identified a multigenerational family with dominantly inherited IBGC and, in 24 members of this family, performed a whole-genome scan using polymorphic microsatellite markers to identify the first chromosomal locus for this disorder (IBGC1). A maximum two-point LOD score of 3.37 was obtained at marker D14S1014, and a maximum multipoint LOD score of 4.95 was obtained between D14S75 and D14S306. The minimal haplotype shared by affected patients extended over a 17.1-cM region bounded by D14S70 and D14S66, which is potentially further narrowed to a 13.3-cM region by a recombination observed in a patient with probable affected status. The age at onset appeared to be decreasing by an average of >20 years with each transmission, which is consistent with genetic anticipation.
Geschwind
D H
DH
Neurogenetics Program, UCLA School of Medicine, Los Angeles, CA 90095-1769, USA. dhg@ucla.edu
Loginov
M
M
Stern
J M
JM
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D020132:Anticipation, Genetic; D001480:Basal Ganglia Diseases / Q000235:genetics* / Q000503:physiopathology; D002114:Calcinosis / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic / Q000235:genetics