A large multi-institutional research effort was started at Yale University in 1993 for the investigation of molecular genetics of inherited cerebrovascular diseases. Our initial efforts have concentrated on the genetics of cerebral cavernous malformations (CCM). Our preliminary results have localized a gene responsible for CCM on the long arm of chromosome 7 and have revealed that CCM is due to inheritance of the identical mutation by descent from the same founder in all Hispanic cases with positive family history.
We are currently testing the candidate genes that are localized to the region that the CCM gene maps on 7q in order to identify the gene responsible for CCM. To date 335 patients including 21 large families have been recruited in collaboration with 11 centers throughout the U.S. A similar but larger study is being carried out to elucidate the molecular genetics predisposing to the formation and rupture of intracranial aneurysms. For this study, in collaboration with 15 centers, we have interviewed over 1,000 patients and have identified more than 60 families with multiple affected members. A genome wide linkage study is currently underway to identify the genetic loci responsible for the formation and/or rupture of these lesions.
Molecular genetic studies of this magnitude require collaboration with multiple centers. We are currently seeking additional sporadic and familial cases from all ethnic backgrounds either with CCM or intracranial aneurysms. Patients who are referred to these studies will be asked to participate in a letter or phone interview after approval of the referring physician.Following this interview, if the patients prove to be important for the study, an informed consent is obtained and blood sample (20 cc from adults, 5-10 cc from children) is collected for genetic studies. The results of these studies are then communicated back to the referring physician. As a part of our collaborative effort we will, of course, include each referring physician as an author on resulting manuscripts.
If you would like to refer patients for either study or have any questions, please call one of the principal investigators: Murat Gunel, MD (203) 737-2677, Issam A. Awad, MD (203) 737-2096 or Richard P. Lifton, MD, PhD (203) 737-4420. Our fax numbers are (203) 624-8213 or (203) 785-6916. These study protocols have been approved by the Human Investigation Committee at Yale University (Protocol #7680).