NOTCH3 mutations in a cohort of Portuguese patients within CADASIL spectrum phenotype

Almeida, Maria Rosário; Elias, Inês; Fernandes, C.; Machado, Rita; Galego, Orlando; Santo, Gustavo

doi:10.1007/s10048-021-00679-w

Cited by 7 publications

(8 citation statements)

References 65 publications

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“…14 An analysis of 24 Portuguese families revealed that the most common NOTCH3 culprit mutations occur in exons 4,8, and 11. 15 This case emphasizes optic nerve involvement as a feature of CADASIL, possibly reflecting an inflammatory process associated with this hereditary vasculopathy. The fact that this may be an isolated presenting feature, as in our patient, poses challenges in the differential diagnosis with other betterestablished etiologies that also show a positive response to immunosuppressive therapy.…”

Section: Discussionmentioning

confidence: 85%

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Inflammatory Optic Neuropathy as a Presenting Feature of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Moura

Pinto

et al. 2022

The Neurohospitalist

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Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly associated with early-onset stroke, migraine and vascular dementia. However, optic nerve involvement has been previously recognised. Results: We report a case of a 21-year-old female presenting with right inferior temporal scotoma, dyschromatopsia, relative pupillary afferent defect and bilateral disk oedema in the fundoscopic examination. Visual evoked potential latencies were bilaterally increased, suggesting optic neuropathy. Cerebrospinal fluid (CSF) evaluation showed 11 leukocytes, .45 mg/dL proteins, elevated IgG (4.55 mg/dL) and 2 oligoclonal bands (OCB) restricted to the CSF. ESR was 17 mm/h and CRP 5 mg/dL. Anti-Aquaporin4 anti-MOG antibodies were negative. The MRI showed right optic nerve hyperintensity, enhancing after the administration of contrast product, and multiple FLAIR focal lesions present throughout the white matter, with a noticeable confluence in the anterior temporal horns. She improved after IV high-dose methylprednisolone. Because the lesions of the white matter were highly atypical for an inflammatory disease and highly suggestive of CADASIL genetic testing was requested. A heterozygous pathogenic variant c994C>T p (Arg332Cys) in the exon 6 of the NOTCH3 gene, compatible with the diagnosis of CADASIL was found. Conclusions: This case highlights isolated optic nerve involvement as a presenting feature of CADASIL, possibly reflecting an inflammatory process associated with this hereditary vasculopathy.

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Section: Discussionmentioning

confidence: 85%

“…14 An analysis of 24 Portuguese families revealed that the most common NOTCH3 culprit mutations occur in exons 4,8, and 11. 15…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Optic Neuropathy as a Presenting Feature of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Moura

Pinto

et al. 2022

The Neurohospitalist

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“…The spectrum of NOTCH3 variants in CADASIL patients and clinical features associated with them have been studied only in a few studies focusing mainly on Asian 5,12-14 and some South-European 4,15,16 populations. The aim of this study was to retrospectively investigate with an unknown effect in intron 15.…”

Section: Discussionmentioning

confidence: 99%

“…The spectrum of NOTCH3 variants in CADASIL patients and clinical features associated with them have been studied only in a few studies focusing mainly on Asian 5 , 12 , 13 , 14 and some South‐European 4 , 15 , 16 populations. The aim of this study was to retrospectively investigate the prevalence of different NOTCH3 variants in Finnish CADASIL patients and examine whether there are phenotypic differences between carriers of different variants.…”

Section: Discussionmentioning

confidence: 99%

Clinical features and spectrum of NOTCH3 variants in Finnish patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Mönkäre

Kuuluvainen

Schleutker

et al. 2022

Acta Neuro Scandinavica

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Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by pathogenic variants in the NOTCH3 gene. In Finland, the majority of CADASIL patients carry the pathogenic founder variant c.397C>T, (p.Arg133Cys), but the spectrum of other NOTCH3 variants has not been investigated previously. The aim of the study was to investigate the spectrum and prevalence of NOTCH3 variants Finnish CADASIL patients and to examine the clinical features associated with them. Materials and Methods:The spectrum of NOTCH3 variants and the clinical features associated with them were retrospectively examined in 294 Finnish CADASIL patients

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“…[ 2 ] The NOTCH3 gene encodes a membrane-bound receptor protein, and to date, several different NOTCH3 gene mutations have been identified. [ 3 ] Here, we report a case of CADASIL with a heterozygous mutation c.931T > G (thymine > guanine) on the exon region of the NOTCH3 gene, resulting in an amino acid change p.C311G (cysteine > glycine).…”

mentioning

confidence: 99%

Case report: Mild leukoencephalopathy caused by a new mutation of NOTCH3 gene

2023

Medicine

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Background: Cerebral autosomal dominant arteriosis with subcortical infarction and leukoencephalopathy (CADASIL) is a single-gene small-vessel disease of the brain characterized by migraine, recurrent ischemic stroke, psychiatric disorders, progressive cognitive decline, and occasional intracerebral hemorrhage. [ 1 ] NOTCH3 was identified as a pathogenic gene for CADASIL. [ 2 ] The NOTCH3 gene encodes a membrane-bound receptor protein, and to date, several different NOTCH3 gene mutations have been identified. [ 3 ] Here, we report a case of CADASIL with a heterozygous mutation c.931T > G (thymine > guanine) on the exon region of the NOTCH3 gene, resulting in an amino acid change p.C311G (cysteine > glycine). Case report: We report a case of a female patient with CADASIL whose genetic sequencing revealed a mutation in the NOTCH3 gene. However, this patient did not exhibit any of the typical clinical findings of CADASIL but the patient’s cerebral magnetic resonance imaging was consistent with the characteristic findings of CADASIL. Conclusions: This case reminds us that mutations caused by different mutation sites present different clinical symptoms.

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NOTCH3 mutations in a cohort of Portuguese patients within CADASIL spectrum phenotype

Cited by 7 publications

References 65 publications

Inflammatory Optic Neuropathy as a Presenting Feature of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Inflammatory Optic Neuropathy as a Presenting Feature of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Clinical features and spectrum of NOTCH3 variants in Finnish patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Case report: Mild leukoencephalopathy caused by a new mutation of NOTCH3 gene

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