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Previous Volume 334:946-951 April 11, 1996 Number 15 Next

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ABSTRACT

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, 4x10¹⁰:1). 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.

Source Information

From the Howard Hughes Medical Institute (M.G., K.F., C.N.-W., R.P.L.), the Section of Neurosurgery (M.G., I.A.A.), and the Departments of Cell Biology (M.G.) and Medicine and Genetics (C.N.-W., R.P.L.), Yale University, New Haven, Conn.; the Departments of Neurosurgery (J.A.A.) and Neurology (L.M.), University of New Mexico, Albuquerque; the Department of Neurosurgery, Stanford University, Palo Alto, Calif. (G.K.S.); the Department of Neurosurgery, Northwestern University, Chicago (H.H.B.); the Department of Neurosurgery, University of Texas Southwestern Medical Center, Dallas (T.A.K.); and the Department of Neurosurgery, University of Southern California, Los Angeles (S.L.G.).

Address reprint requests to Dr. Lifton at Yale University School of Medicine, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, 295 Congress Ave., New Haven, CT 06510.

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