{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T04:21:52Z","timestamp":1780719712229,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["Z171100001017080"],"award-info":[{"award-number":["Z171100001017080"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>There is evidence showing both heterozygous <jats:italic>HTRA1<\/jats:italic> and homozygous <jats:italic>HTRA1<\/jats:italic> mutations as causal for familial cerebral small vessel disease (CSVD). The clinical and neuroimaging signs of heterozygous <jats:italic>HTRA1<\/jats:italic>\u2010related CSVD can mimic cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to characterize the genotypic and phenotypic features of <jats:italic>HTRA1<\/jats:italic>\u2010related CSVD, and we compared the features of heterozygous <jats:italic>HTRA1<\/jats:italic>\u2010related CSVD and CADASIL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We carried out genetic sequencing in a series of unrelated patients with suspected familial CSVD from China. Clinical and imaging characteristics of heterozygous <jats:italic>HTRA1<\/jats:italic>\u2010related CSVD and CADASIL were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified nine heterozygous <jats:italic>HTRA1<\/jats:italic> mutations and one homozygous <jats:italic>HTRA1<\/jats:italic> mutation, seven of which are novel. Compared with CADASIL, patients with heterozygous <jats:italic>HTRA1<\/jats:italic>\u2010related CSVD had a higher proportion of spine disorders and a lower proportion of white matter hyperintensities involving the anterior temporal lobe (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This study shows that most <jats:italic>HTRA1<\/jats:italic>\u2010related CSVD patients in China carry heterozygous <jats:italic>HTRA1<\/jats:italic> mutations. The specific extra\u2010neurological features and neuroimaging features reveal informative differences between heterozygous <jats:italic>HTRA1<\/jats:italic>\u2010related CSVD and CADASIL. We expand the mutational spectrum of <jats:italic>HTRA1<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51654","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T13:43:42Z","timestamp":1662039822000},"page":"1586-1595","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel mutations in <scp><i>HTRA1<\/i><\/scp>\u2010related cerebral small vessel disease and comparison with <scp>CADASIL<\/scp>"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-6572","authenticated-orcid":false,"given":"Chen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University  Beijing 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Disease Research Center for Neurological Disorders Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research Institute of Neuroscience, School of Medicine, Xiamen University  Xiamen Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songtao","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0356-3584","authenticated-orcid":false,"given":"Zaiqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, China National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital, Capital Medical University  Beijing 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