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Leukodystrophy - adult onset

Gene: NOTCH3

Green List (high evidence)
NOTCH3 (notch 3)
EnsemblGeneIds (GRCh38): ENSG00000074181
EnsemblGeneIds (GRCh37): ENSG00000074181
OMIM: 600276, Gene2Phenotype
NOTCH3 is in 13 panels

2 reviews

Ain Roesley (Victorian Clinical Genetics Services)

Green List (high evidence)

Pre-print
Review of research and diagnostic databases and literature review found 50 individuals from 31 families with biallelic variants.

13 PTCS (including splice) and 15 missense resulting in gain or loss of Cys residue.

AR PTCs are associated with early onset leukoencephalopathy including cognitive decline, dev delay/ID and dysmorphism

AR missense are associated with later onset (compared to AR PTVs) CADASIL-like phenotype. Similar severity and variability as AD CADASIL, difference is age of onset. Mid-adulthood for AD and early-adulthood for AR
Created: 30 Apr 2024, 5:54 a.m. | Last Modified: 30 Apr 2024, 5:54 a.m.
Panel Version: 0.137

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310

Variants in this GENE are reported as part of current diagnostic practice

Created: 30 Apr 2024, 5:54 a.m.
Last Modified: 30 Apr 2024, 5:54 a.m.
Panel version: 0.137

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Adult onset.
Created: 9 May 2020, 7:36 a.m. | Last Modified: 9 May 2020, 7:36 a.m.
Panel Version: 0.57

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, MIM# 125310

Created: 9 May 2020, 7:36 a.m.
Last Modified: 9 May 2020, 7:36 a.m.
Panel version: 0.57

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Royal Melbourne Hospital
Phenotypes
  • neurodevelopmental disorder MONDO:0700092, NOTCH3-related
  • Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310
OMIM
600276
Clinvar variants
Variants in NOTCH3
Penetrance
None
Panels with this gene

History Filter Activity

30 Apr 2024, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: NOTCH3 were changed from neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310

30 Apr 2024, Gel status: 3

Set Phenotypes

Ain Roesley (Victorian Clinical Genetics Services)

Phenotypes for gene: NOTCH3 were changed from Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, 125310 to neurodevelopmental disorder MONDO:0700092, NOTCH3-related; Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1 MIM#125310

30 Apr 2024, Gel status: 3

Set mode of inheritance

Ain Roesley (Victorian Clinical Genetics Services)

Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

9 May 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: notch3 has been classified as Green List (High Evidence).

9 May 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

30 Dec 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: NOTCH3 was added gene: NOTCH3 was added to Leukodystrophy - adult onset_RMH. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: NOTCH3 were set to Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy 1, 125310