In:
Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 94, No. 1 ( 2023-01), p. 74-81
Abstract:
This study aimed to clarify the frequency and clinical features of monogenic cerebral small vessel disease (mgCSVD) among patients with adult-onset severe CSVD in Japan. Methods This study included patients with adult-onset severe CSVD with an age of onset ≤55 years (group 1) or 〉 55 years and with a positive family history (group 2). After conducting conventional genetic tests for NOTCH3 and HTRA1 , 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. Results Group 1 and group 2 included 75 and 31 patients, respectively. In total, 30 patients had NOTCH3 mutations, 11 patients had HTRA1 mutations, 6 patients had ABCC6 mutations, 1 patient had a TREX1 mutation, 1 patient had a COL4A1 mutation and 1 patient had a COL4A2 mutation. The total frequency of mutations in NOTCH3 , HTRA1 and ABCC6 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). Conclusions More than 90% of mgCSVDs were diagnosed by screening for NOTCH3 , HTRA1 and ABCC6 . The target sequences for these three genes may efficiently diagnose mgCSVD in Japanese patients.
Type of Medium:
Online Resource
ISSN:
0022-3050
,
1468-330X
DOI:
10.1136/jnnp-2022-329917
Language:
English
Publisher:
BMJ
Publication Date:
2023
detail.hit.zdb_id:
1480429-3
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