Identification of a Locus on Chromosome 14q for Idiopathic Basal Ganglia Calcification (Fahr Disease)

• Published in: American journal of human genetics Vol. 65; no. 3; pp. 764 - 772
• Main Authors: Geschwind, Daniel H., Loginov, Maxim, Stern, John M.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-09-1999; University of Chicago Press
• Subjects: Adolescent; Adult; Age of Onset; Aged; Anticipation; Anticipation, Genetic; Basal Ganglia Diseases - genetics; Basal Ganglia Diseases - physiopathology; Biological and medical sciences; Calcinosis - genetics; Calcinosis - physiopathology; Cerebral calcification; Child; Child, Preschool; Chromosome Mapping; Chromosomes, Human, Pair 14 - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dystonia; Female; Genes, Dominant; Genetic linkage; Haplotypes - genetics; Humans; Lod Score; Male; Medical sciences; Microsatellite Repeats - genetics; Middle Aged; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - physiopathology; Neurology; Parkinsonism; Pedigree; Polymorphism, Genetic; Recombination, Genetic - genetics; Striatopallidodentate calcinosis; Parkinsonism; Cerebral calcification; Anticipation; Dystonia; Genetic linkage; Striatopallidodentate calcinosis; Human; Nervous system diseases; Family study; Pathogenesis; Idiopathic; Chromosome D14; Basal ganglion; Genetic determinism; Fahr disease; Cerebral disorder; Genetic disease; Phenotype; Gene; Autosomal character; Central nervous system disease; Calcification; Degenerative disease; Dominant character; Locus; Haplotype
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/302558

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.