TY - JOUR
T1 - Genetic linkage of Paget disease of the bone to chromosome 18q
AU - Cody, J. D.
AU - Singer, F. R.
AU - Roodman, G. D.
AU - Otterund, B.
AU - Lewis, T. B.
AU - Leppert, M.
AU - Leach, R. J.
N1 - Funding Information:
We would like to thank the MacDonald family fund and Microsoft Corporation for their generous support of this work. This study was funded, in part, by a pilot grant program of the Aging Research and Education Center at the University of Texas Health Science Center at San Antonio (grant 1P30AG1319), by the W. M. Keck Foundation and the Garcia Bremer Research Fund, and by NIH grant P01AR39529 (to G.D.R).
PY - 1997/11
Y1 - 1997/11
N2 - Paget disease is a common bone disease characterized by abnormal osteoclasts that are large, multinucleated, and overactive and that contain paramyxovirus-like nuclear inclusions. There is evidence for a major genetic component to Paget disease, with up to 40% of patients having affected first- degree relatives; however, the locus (loci) and gene(s) involved are unknown. Another bone disorder, familial expansile osteolysis (FEO), although extremely rare, also is characterized by similar osteoclast abnormalities but has an earlier age at onset and a more aggressive clinical progression. The causative gene for FEO has been localized to a region of human chromosome 18q. On the basis of the presence of similar clinical findings and of vital- like nuclear inclusions in osteoclasts, we hypothesized that FEO and Paget disease are allelic versions of the same locus. Therefore, a large kindred with a high incidence of Paget disease was examined to determine if Paget disease was linked to genetic markers in the same region of chromosome 18 as that for FEO. Our analysis yielded a two-point LOD score of 3.40, with the genetic marker D18S42, a marker tightly linked to the FEO locus. This demonstrates that the gene(s) responsible for FEO and that for Paget disease are either closely linked or the same locus.
AB - Paget disease is a common bone disease characterized by abnormal osteoclasts that are large, multinucleated, and overactive and that contain paramyxovirus-like nuclear inclusions. There is evidence for a major genetic component to Paget disease, with up to 40% of patients having affected first- degree relatives; however, the locus (loci) and gene(s) involved are unknown. Another bone disorder, familial expansile osteolysis (FEO), although extremely rare, also is characterized by similar osteoclast abnormalities but has an earlier age at onset and a more aggressive clinical progression. The causative gene for FEO has been localized to a region of human chromosome 18q. On the basis of the presence of similar clinical findings and of vital- like nuclear inclusions in osteoclasts, we hypothesized that FEO and Paget disease are allelic versions of the same locus. Therefore, a large kindred with a high incidence of Paget disease was examined to determine if Paget disease was linked to genetic markers in the same region of chromosome 18 as that for FEO. Our analysis yielded a two-point LOD score of 3.40, with the genetic marker D18S42, a marker tightly linked to the FEO locus. This demonstrates that the gene(s) responsible for FEO and that for Paget disease are either closely linked or the same locus.
UR - http://www.scopus.com/inward/record.url?scp=0030732102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030732102&partnerID=8YFLogxK
U2 - 10.1086/301601
DO - 10.1086/301601
M3 - Article
C2 - 9345096
AN - SCOPUS:0030732102
SN - 0002-9297
VL - 61
SP - 1117
EP - 1122
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -