Adult onset leukodystrophy

Gene: NPC1

Amber List (moderate evidence)

NPC1 (NPC intracellular cholesterol transporter 1)
EnsemblGeneIds (GRCh38): ENSG00000141458
EnsemblGeneIds (GRCh37): ENSG00000141458
OMIM: 607623, Gene2Phenotype
NPC1 is in 20 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

Comment on list classification: There are two unrelated cases associating NPC1 with white matter abnormalities in adulthood. However, there are several other cases with childhood-onset and functional evidence from animal models. This gene should be rated AMBER and 'watchlist' tag should be added.
Created: 30 May 2023, 5:56 p.m. | Last Modified: 30 May 2023, 5:56 p.m.
Panel Version: 3.8
As reviewed by Zornitza Stark, five out of 11 patients reported with Niemann-Pick Disease Type C in PMID:26910362 had white matter lesions. Of these five, only one had adult-onset.

PMID:27900365 reported an adult-onset Niemann-Pick disease type C patient that had mild white matter loss.

Functional studies from NPC1 knockout mouse model also support the association of NPC1 with white matter abnormalities (PMIDs: 29406968 & 31254056).

This gene has been associated with Niemann-Pick disease in both OMIM and Gene2Phenotype.
Created: 30 May 2023, 5:52 p.m. | Last Modified: 30 May 2023, 5:52 p.m.
Panel Version: 3.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Niemann-Pick disease, type C1, OMIM:257220; Niemann-Pick disease, type D, OMIM:257220

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

White matter lesions identified in MRI of 5/11 of Niemann-Pick patients (including adult-onset) and in an NPC mouse model.
Sources: Expert list
Created: 21 Jun 2020, 6:33 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Niemann-Pick disease, type C1/D 257220

Publications

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

History Filter Activity

30 May 2023, Gel status: 2

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag watchlist tag was added to gene: NPC1.

30 May 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: npc1 has been classified as Amber List (Moderate Evidence).

30 May 2023, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: NPC1 were set to 26910362; 29406968

21 Jun 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: NPC1 was added gene: NPC1 was added to White matter disorders - adult onset. Sources: Expert list Mode of inheritance for gene: NPC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NPC1 were set to 26910362; 29406968 Phenotypes for gene: NPC1 were set to Niemann-Pick disease, type C1/D 257220 Review for gene: NPC1 was set to GREEN gene: NPC1 was marked as current diagnostic