TY - JOUR
T1 - Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease)
AU - Geschwind, Daniel H.
AU - Loginov, Maxim
AU - Stern, John M.
N1 - Funding Information:
This study was partially supported by a grant from the Dystonia Medical Research Foundation (G3185). We thank Stanley F. Nelson, M.D. for helpful discussions in the initial characterization of this family for genetic study, as well as Robert C. Collins, M.D. for his support of the Neurogenetics Program. We also thank Maria Jesus Sobrido, M.D., Ph.D. for helpful comments on the manuscript. We are indebted to the family members who participated and to the many primary physicians who aided in collecting information and in characterizing family members. We also acknowledge Bonita Porch for her editorial assistance.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0033358650
U2 - 10.1086/302558
DO - 10.1086/302558
M3 - Article
C2 - 10441584
AN - SCOPUS:0033358650
SN - 0002-9297
VL - 65
SP - 764
EP - 772
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -