TABLE 3.
Clinical features of the patients with rare NOTCH3 variants and deposition of GOM in skin biopsy, and/or neuropathological autopsy data available
| c.341‐2A>G | c.391G>T,p.(Gly131Cys) | c.1012T>A,p.(Cys338Ser) | c.1300_1308dupGAGTGTCTG,p.(Glu434_Leu436dup) | c.1660G>T,p.(Gly528Cys) | c.1660G>T,p.(Gly528Cys) | c.3226C>T,p.(Arg1076Cys) | c.6102dup,p.(Gly2035Argfs*60) | |
|---|---|---|---|---|---|---|---|---|
| Patient | C6 | C7 | C19 | C21 | C28 | C29 | C38 | C42 |
| Sex | F | F | M | M | F | F | F | F |
| Age at onset | 52 | 35 | 40 | 49 | 59 | 50? | 45 | 52 |
| Age at death | 62 | 44 | 68 | 87 | ||||
| Source of clinical information | Medical records | Referral | Medical records | Medical records | Medical records | Medical records | Referral and skin biopsy report | Medical records |
| WM changes in MRI | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Migraine/headache | Yes | n/a | Yes | No | n/a | Yes | n/a | No |
| Ischemic stroke/TIA | Yes | n/a | No | Yes | n/a | n/a | Yes | n/a |
| ICH | No | n/a | No | No | Yes | No | n/a | No |
| Epilepsy | No | n/a | Yes | No | No | Yes | n/a | No |
| Psychiatric symptom | No | n/a | n/a | n/a | Yes | Yes | n/a | Yes |
| Cognitive impairment | Yes | n/a | No | No | Yes | Yes | n/a | Yes |
| Hypertension | Yes | n/a | Yes | Yes | n/a | n/a | No | n/a |
| Hyperlipidemia | Yes | n/a | No | Yes | n/a | n/a | No | n/a |
| Smoking | No | n/a | No | Yes | n/a | n/a | No | n/a |
| Diabetes | No | n/a | No | No | n/a | n/a | No | n/a |
| Family history | Yes | n/a | n/a | Yes | Yes | n/a | n/a | Yes |
| Skin biopsy | GOM+ | GOM+ | Not performed | GOM+ | GOM+ | GOM+ | GOM+ | GOM+ |
| Neuropathology | Lacunar infarcts, WM changes, thickened arterioles; vascular changes consistent with CADASIL. Purkinje cell loss in cerebellum, gliotic foci in hippocampus | Lacunar infarcts, WM changes; most prominent lesions in basal ganglia. Thickened vessels, especially arterioles, consistent with CADASIL. Findings milder than usually found in CADASIL patients | WM changes, multiple infarcts in basal ganglia, infarcts in nucleus caudatus and putamen. Thickened vessels, especially arterioles, consistent with CADASIL. Ischemic lesion in cerebellum, AD changes in temporal lobe, β‐amyloid positivity, Braak II. |
Abbreviations: AD, Alzheimer's disease; F, female; GOM, granular osmiophilic material; ICH, intracerebral hemorrhage; M, male; n/a, information not available or not applicable; TIA, transient ischemic attack; WM, white matter.