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After conducting conventional genetic tests for<jats:italic>NOTCH3<\/jats:italic>and<jats:italic>HTRA1<\/jats:italic>, whole-exome sequencing was performed on undiagnosed patients. Patients were divided into two groups according to the results of the genetic tests: monogenic and undetermined. The clinical and imaging features were compared between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Group 1 and group 2 included 75 and 31 patients, respectively. In total, 30 patients had<jats:italic>NOTCH3<\/jats:italic>mutations, 11 patients had<jats:italic>HTRA1<\/jats:italic>mutations, 6 patients had<jats:italic>ABCC6<\/jats:italic>mutations, 1 patient had a<jats:italic>TREX1<\/jats:italic>mutation, 1 patient had a<jats:italic>COL4A1<\/jats:italic>mutation and 1 patient had a<jats:italic>COL4A2<\/jats:italic>mutation. The total frequency of mutations in<jats:italic>NOTCH3<\/jats:italic>,<jats:italic>HTRA1<\/jats:italic>and<jats:italic>ABCC6<\/jats:italic>was 94.0% in patients with mgCSVD. In group 1, the frequency of a family history of first relatives, hypertension and multiple lacunar infarctions (LIs) differed significantly between the two groups (monogenic vs undetermined; family history of first relatives, 61.0% vs 25.0%, p=0.0015; hypertension, 34.1% vs 63.9%, p=0.0092; multiple LIs, 87.8% vs 63.9%, p=0.0134).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>More than 90% of mgCSVDs were diagnosed by screening for<jats:italic>NOTCH3<\/jats:italic>,<jats:italic>HTRA1<\/jats:italic>and<jats:italic>ABCC6<\/jats:italic>. The target sequences for these three genes may efficiently diagnose mgCSVD in Japanese patients.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2022-329917","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T17:25:38Z","timestamp":1666200338000},"page":"74-81","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["High frequency of<i>HTRA1<\/i>AND<i>ABCC6<\/i>mutations in Japanese patients with adult-onset cerebral small vessel 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