Abstract | BACKGROUND AND PURPOSE: METHODS: Mutational analyses of HTRA1 were performed by Sanger sequencing in 222 subjects, selected from a cohort of 337 unrelated patients with SVD after excluding those harboring a NOTCH3 mutation. The influence of these mutations on HTRA1 protease activities was characterized. RESULTS: Seven novel heterozygous mutations in HTRA1 were identified, including p.Gly120Asp, p.Ile179Asn, p.Ala182Profs*33, p.Ile256Thr, p.Gly276Ala, p.Gln289Ter, and p.Asn324Thr, and each was identified in 1 single index patient. All mutations significantly compromise the HTRA1 protease activities. For the 7 index cases and another 2 affected siblings carrying a heterozygous HTRA1 mutation, the common clinical presentations include lacunar infarction, intracerebral hemorrhage, cognitive decline, and spondylosis at the fifth to sixth decade of life. Among the 9 patients, 4 have psychiatric symptoms as delusion, depression, and compulsive behavior, 3 have leukoencephalopathy in anterior temporal poles, and 2 patients have alopecia. CONCLUSIONS: Heterozygous HTRA1 mutations account for 2.08% (7 of 337) of SVD in Taiwan. The clinical and neuroradiological features of HTRA1-related SVD and sporadic SVD are similar. These findings broaden the mutational spectrum of HTRA1 and highlight the pathogenic role of heterozygous HTRA1 mutations in SVD.
|
Authors | Yi-Chung Lee, Chih-Ping Chung, Nai-Chen Chao, Jong-Ling Fuh, Feng-Chi Chang, Bing-Wing Soong, Yi-Chu Liao |
Journal | Stroke
(Stroke)
Vol. 49
Issue 7
Pg. 1593-1601
(07 2018)
ISSN: 1524-4628 [Electronic] United States |
PMID | 29895533
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2018 American Heart Association, Inc. |
Chemical References |
- High-Temperature Requirement A Serine Peptidase 1
- HtrA1 protein, human
|
Topics |
- Alopecia
(genetics)
- Cerebral Small Vessel Diseases
(genetics)
- DNA Mutational Analysis
- Female
- Heterozygote
- High-Temperature Requirement A Serine Peptidase 1
(genetics)
- Humans
- Leukoencephalopathies
(genetics)
- Male
- Mental Disorders
(genetics)
- Mutation
- Taiwan
|