From the Population Health Research Institute, Hamilton, Ontario, Canada (M.C., S.Y., G.P.); HRB Clinical Research Facility, NUI Galway, University Hospital Galway, Ireland (M.O.); Vlaams Instituut voor Biotechnologie, Vesalius Research Center, Department of Neurology, University Hospitals KU Leuven, Belgium (V.T.); Philippine General Hospital, Manila (A.D.); Fundación Oftalmológica de Santander, Medical School, Universidad de Santander, Bucaramanga, Colombia (P.L.-J., D.G.-A.); Division of Cardiology, Uganda Heart Institute, Kampala (C.M.); 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (A.C., M.S.); Department of Pharmacology, Medical University of Warsaw, Poland (A.C., M.S.); and Iranian Center of Neurological Research, Tehran University of Medical Sciences, Iran (S.O.).
Stroke. 2017 Aug;48(8):2263-2265. doi: 10.1161/STROKEAHA.117.017322. Epub 2017 Jul 5.
Mendelian strokes are rare genetic disorders characterized by early-onset small-vessel stroke. Although extensively studied among families with syndromic features, whether these genes affect risk among sporadic cases is unknown.
We sequenced 8 genes responsible for Mendelian stroke in a case-control study of sporadic stroke cases (≤70 years). Participants included 1251 primary stroke cases of small-vessel pathology (637 intracerebral hemorrhage and 614 small-vessel ischemic stroke cases) and 1716 controls from the INTERSTROKE study (Study of the Importance of Conventional and Emerging Risk Factors of Stroke in Different Regions and Ethnic Groups of the World).
Overall, the prevalence of canonical disease-causing mutations was 0.56% in cases and 0.23% in controls (odds ratio=1.89; 95% confidence interval, 0.54-7.57; =0.33). CADASIL (Cerebral Autosomal Dominant Arteriopathies with Subcortical Infarcts and Leukoencephalopathies) mutations were more frequent among cases (0.48%) than controls (0.23%) but were not significantly associated with stroke risk (odds ratio=2.03; 95% confidence interval, 0.58-8.02; =0.27). Next, we included all rare nonsynonymous mutations to investigate whether other types of mutations may contribute to stroke risk. Overall, 13.5% of cases and 14.2% of controls were carriers of at least one rare nonsynonymous mutation among the 8 Mendelian stroke genes. Mutation carriers were not at elevated risk of stroke (odds ratio=0.93; 95% confidence interval, 0.75-1.16; =0.55).
In the absence of syndromic features and family history of stroke, screening for Mendelian mutations among small-vessel stroke patients is unlikely to have high diagnostic utility.
孟德尔氏中风是一种罕见的遗传性疾病，其特征为早发性小血管中风。尽管在有综合征特征的家族中进行了广泛研究，但这些基因是否会影响散发性病例的风险尚不清楚。
我们在一项散发性中风病例（≤70 岁）的病例对照研究中对 8 个导致孟德尔氏中风的基因进行了测序。参与者包括来自 INTERSTROKE 研究（不同地区和种族人群中风常规和新兴危险因素的研究）的 1251 例小血管病变原发性中风病例（637 例脑出血和 614 例小血管缺血性中风病例）和 1716 例对照。
总体而言，病例组中典型致病突变的患病率为 0.56%，对照组为 0.23%（比值比=1.89；95%置信区间，0.54-7.57；=0.33）。CADASIL（伴有皮质下梗死和白质脑病的常染色体显性脑动脉病）突变在病例组中更为常见（0.48%），而对照组中则较少（0.23%），但与中风风险无显著相关性（比值比=2.03；95%置信区间，0.58-8.02；=0.27）。接下来，我们纳入了所有罕见的非同义突变，以研究其他类型的突变是否可能导致中风风险增加。总体而言，在 8 个孟德尔氏中风基因中，有 13.5%的病例和 14.2%的对照携带至少一种罕见的非同义突变。突变携带者中风风险并未升高（比值比=0.93；95%置信区间，0.75-1.16；=0.55）。
在没有中风综合征特征和家族史的情况下，对小血管中风患者进行孟德尔突变筛查不太可能具有高诊断效用。
