TY - JOUR
T1 - A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans
AU - Gunel, Murat
AU - Awad, Issam A.
AU - Finberg, Karin
AU - Anson, John A.
AU - Steinberg, Gary K.
AU - Batjer, H. Hunt
AU - Kopitnik, Thomas A.
AU - Morrison, Leslie
AU - Giannotta, Steven L.
AU - Nelson-Williams, Carol
AU - Lifton, Richard P.
PY - 1996/4/11
Y1 - 1996/4/11
N2 - Background. Cerebral cavernous malformation is a vascular disease of the brain causing headaches, seizures, and cerebral hemorrhage. Familial and sporadic cases are recognized, and a gene causing familial disease has been mapped to chromosome 7. Hispanic Americans have a higher prevalence of cavernous malformation than do other ethnic groups, raising the possibility that affected persons in this population have inherited the same mutation from a common ancestor. Methods. We compared the segregation of genetic markers and clinical cases of cavernous malformation in Hispanic-American kindreds with familial disease; we also compared the alleles for markers linked to cavernous malformation in patients with familial and sporadic cases. Results. All kindreds with familial disease showed linkage of cavernous malformation to a short segment of chromosome 7 (odds supporting linkage, 4x10 10:1). Forty-seven affected members of 14 kindreds shared identical alleles for up to 15 markers linked to the cavernous-malformation gene, demonstrating that they had inherited the same mutation from a common ancestor. Ten patients with sporadic cases also shared these same alleles, indicating that they too had inherited the same mutation. Thirty-three asymptomatic carriers of the disease gene were identified, demonstrating the variability and age dependence of the development of symptoms and explaining the appearance of apparently sporadic cases. Conclusions. Virtually all cases of familial and sporadic cavernous malformation among Hispanic Americans of Mexican descent are due to the inheritance of the same mutation from a common ancestor.
AB - Background. Cerebral cavernous malformation is a vascular disease of the brain causing headaches, seizures, and cerebral hemorrhage. Familial and sporadic cases are recognized, and a gene causing familial disease has been mapped to chromosome 7. Hispanic Americans have a higher prevalence of cavernous malformation than do other ethnic groups, raising the possibility that affected persons in this population have inherited the same mutation from a common ancestor. Methods. We compared the segregation of genetic markers and clinical cases of cavernous malformation in Hispanic-American kindreds with familial disease; we also compared the alleles for markers linked to cavernous malformation in patients with familial and sporadic cases. Results. All kindreds with familial disease showed linkage of cavernous malformation to a short segment of chromosome 7 (odds supporting linkage, 4x10 10:1). Forty-seven affected members of 14 kindreds shared identical alleles for up to 15 markers linked to the cavernous-malformation gene, demonstrating that they had inherited the same mutation from a common ancestor. Ten patients with sporadic cases also shared these same alleles, indicating that they too had inherited the same mutation. Thirty-three asymptomatic carriers of the disease gene were identified, demonstrating the variability and age dependence of the development of symptoms and explaining the appearance of apparently sporadic cases. Conclusions. Virtually all cases of familial and sporadic cavernous malformation among Hispanic Americans of Mexican descent are due to the inheritance of the same mutation from a common ancestor.
UR - http://www.scopus.com/inward/record.url?scp=15844411517&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=15844411517&partnerID=8YFLogxK
U2 - 10.1056/NEJM199604113341503
DO - 10.1056/NEJM199604113341503
M3 - Article
C2 - 8596595
AN - SCOPUS:15844411517
SN - 0028-4793
VL - 334
SP - 946
EP - 951
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 15
ER -