A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans

N Engl J Med. 1996 Apr 11;334(15):946-51. doi: 10.1056/NEJM199604113341503.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Neoplasms / genetics*
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 7*
  • Female
  • Genetic Linkage
  • Hemangioma, Cavernous / genetics*
  • Hispanic Americans / genetics*
  • Humans
  • Intracranial Arteriovenous Malformations / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree