A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans
A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans
复制标题
DOI：
10.1056/nejm199604113341503
复制
发表时间：
1996-04-11
影响因子：
158.5
通讯作者：
Lifton, RP
中科院分区：
文献类型：
--
作者：
Gunel, M;Awad, IA;Lifton, RP
背景资料。脑海绵状血管畸形是一种引起头痛、癫痫发作和脑出血的脑血管疾病。家族性和散发性病例被确认，导致家族性疾病的基因被定位在7号染色体上。拉美裔美国人比其他民族有更高的海绵状畸形患病率，这增加了该人群中受影响的人从共同祖先那里遗传相同突变的可能性。我们比较了有家族疾病的西班牙裔美国人家族中海绵状畸形遗传标记的分离和临床病例；我们还比较了与海绵状畸形相关的标记在家族性和散发性病例中的等位基因。所有家族性疾病家系均显示海绵状畸形与7号染色体的一小段连锁(优势支持连锁，4×10(10)：1)，14个家系的47名受累成员拥有多达15个与海绵状畸形基因连锁的相同等位基因，表明他们从共同的祖先那里遗传了相同的突变。10名零星病例的患者也分享了这些相同的等位基因，这表明他们也遗传了相同的突变。共发现33例无症状携带者，证实了症状发展的变异性和年龄依赖性，并解释了明显的散发性病例的出现。在墨西哥裔西班牙裔美国人中，几乎所有的家族性和散发性海绵状畸形病例都是由于从共同祖先那里继承了相同的突变。(C)1996年，马萨诸塞州医学会。
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. (C) 1996, Massachusetts Medical Society.