Hereditary neuropathy or pain disorder

Gene: PLP1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 1:11 p.m. | Last Modified: 26 Sep 2024, 1:11 p.m.

Panel Version: 5.16

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Green List (high evidence)

Numerous PLP1 variants have been associated with OMIM:312080 and OMIM:312920. This gene should be green on this panel, as the panel scope now includes complex phenotypes.

Created: 13 May 2024, 8:57 a.m. | Last Modified: 13 May 2024, 8:57 a.m.

Panel Version: 4.11

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Spastic paraplegia 2, X-linked, OMIM:312920; Pelizaeus-Merzbacher disease, OMIM:312080

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: Pelizaeus-Merbacher/Spastic paraplegia 2 - is neuropathy a feature?

Created: 7 Dec 2019, 12:03 a.m. | Last Modified: 7 Dec 2019, 12:03 a.m.

Panel Version: 0.86

This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.

Created: 6 Dec 2019, 10:25 p.m. | Last Modified: 6 Dec 2019, 10:25 p.m.

Panel Version: 0.84

Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 29 Apr 2019, 12:53 p.m.

Red List (low evidence)

Unable to find any evidence of clear neuropathy association

Created: 29 Apr 2019, 12:30 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Hereditary Neuropathies

Green List (high evidence)

Comment on mode of inheritance: X-linked recessive.

Created: 5 May 2016, 9:25 a.m.

Comment on list classification: Confirmed DD gene for SPASTIC PARAPLEGIA X-LINKED TYPE 2 and LEUKODYSTROPHY HYPOMYELINATING TYPE 1.

Created: 5 May 2016, 9:24 a.m.

Green List (high evidence)

should be included in R78 panel as panel now includes complex phenotypes e.g. ACOX1, HEXA, HEXB, MCM3AP, MORC2, PIGB, POLR3B, SLC25A46

Created: 17 Mar 2024, 9:29 p.m. | Last Modified: 17 Mar 2024, 9:29 p.m.

Panel Version: 3.83

Null mutations cause a neuropathy

Created: 16 May 2019, 8:41 p.m.

Loss of function mutations cause demyelinating neuropathy with spasticity

Created: 9 Dec 2015, 8:50 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 12601703

Not a CMT gene

Created: 8 Dec 2015, 3:06 p.m.