Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CARASIL
Conditions
Interventions
HTRA1 imaging subgroup:None
suspected hCSVD:None
Imaging healthy control group:None
HTRA1-iPSC subgroup:None
iPSC healthy control group:None
Sponsors
Xuanwu Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Part I (HTRA1 genetic screening cohort): (1) Aged 18–80 years, either sex; (2) brain MRI showing at least one marker of cerebral small vessel disease, including a recent small subcortical infarct, lacune, white matter hyperintensity, cerebral microbleed, enlarged perivascular space, or brain atrophy; (3) clinical or family features suggestive of hereditary cerebral small vessel disease, including at least one of the following: ischemic stroke or transient ischemic attack before 50 years of age, moderate-to-severe white matter hyperintensities or multiple lacunes without obvious conventional vascular risk factors, a family history of cerebral small vessel disease, early-onset stroke, early-onset cognitive impairment or gait disturbance, or HTRA1-related manifestations such as premature alopecia, low back pain or spinal degeneration; and (4) written informed consent provided by the participant or legal representative. 2.Part II (multimodal MRI substudy): Participants in the HTRA1 group must meet the inclusion criteria for Part I, carry a pathogenic or likely pathogenic HTRA1 variant confirmed by genetic testing, be able to complete cognitive assessment, quantitative susceptibility mapping and dynamic contrast-enhanced MRI, have renal function suitable for gadolinium-enhanced MRI, and provide written informed consent. Healthy controls must be matched with the HTRA1 group for age, sex and educational level, have no history of stroke or other definite neurological disorders, have cognitive performance within the normal range, be eligible for quantitative susceptibility mapping and dynamic contrast-enhanced MRI, and provide written informed consent. 3.Part III (iPSC-VSMC substudy): Participants in the HTRA1 group must meet the inclusion criteria for Part I, carry a pathogenic or likely pathogenic HTRA1 variant confirmed by genetic testing, have adequate clinical and imaging data, be able to provide sufficient peripheral venous blood for PBMC isolation and iPSC reprogramming, and provide written informed consent covering cell reprogramming, long-term storage and genetic research. Healthy controls will preferably be adult healthy family members who do not carry the proband-specific HTRA1 variant. If no suitable family member is available, age- and sex-matched unrelated healthy volunteers may be recruited. Healthy controls must have no history of stroke, cognitive impairment or other definite neurological disorders, be able to provide sufficient peripheral blood, and provide written informed consent.
Exclusion criteria
Exclusion criteria: 1.Part I (HTRA1 genetic screening cohort): (1) Brain lesions fully explained by non-small-vessel causes, including large-artery atherosclerosis, cardioembolism, vasculitis, inflammatory demyelinating disease, central nervous system infection, toxic or metabolic encephalopathy, or brain tumor; (2) inability to undergo peripheral blood collection or genetic testing; (3) seriously incomplete clinical or imaging data preventing evaluation of the primary outcome; or (4) any other condition considered unsuitable for participation by the investigator. 2.Part II (multimodal MRI substudy; applicable to both the HTRA1 and healthy control groups): (1) Absolute contraindications to MRI, including a cardiac pacemaker or MRI-incompatible metallic implant; (2) severe claustrophobia, marked involuntary movement, or other inability to complete MRI; (3) previous severe hypersensitivity reaction to a gadolinium-based contrast agent; (4) severe renal impairment unsuitable for contrast-enhanced MRI; (5) pregnancy or possible pregnancy; (6) another central nervous system disorder that may substantially affect quantitative susceptibility mapping or blood-brain barrier measurements. 3.Part III (iPSC-VSMC substudy): Participants in either the HTRA1 or healthy control group will be excluded for any of the following: (1) Active hepatitis B, hepatitis C, HIV infection or syphilis; (2) hematological malignancy, severe hematopoietic dysfunction, or recent treatment that may substantially affect peripheral blood cells; (3) current severe infection or systemic inflammatory disease; or (4) insufficient quantity or inadequate quality of peripheral blood for PBMC isolation. Healthy controls will also be excluded if they have clinical or imaging abnormalities suggestive of hereditary cerebral small vessel disease, or a severe genetic, metabolic or immune disorder that may affect interpretation of cellular phenotypes.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Detection rate of pathogenic or likely pathogenic heterozygous HTRA1 variants; | — |
Secondary
| Measure | Time frame |
|---|---|
| HTRA1-related clinical phenotype spectrum;Multimodal magnetic resonance imaging phenotype;Cellular and molecular phenotypes of iPSC-derived vascular smooth muscle cells; | — |
Countries
China
Contacts
Public ContactHaiqing Song
Xuanwu Hospital, Capital Medical University
Outcome results
None listed