Hereditary neuropathy or pain disorder

Gene: SOX10

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (more than six unrelated cases) for the association of monoallelic SOX10 variants with demyelinating peripheral neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 5 Nov 2024, 6:43 p.m. | Last Modified: 5 Nov 2024, 6:43 p.m.

Panel Version: 6.113

PMID:15004559 reported four unrelated individuals with a clinical phenotype consistent with PCWH syndrome. All four individuals had peripheral demyelinating neuropathy as shown by nerve biopsy and nerve conduction studies. They were all identified with three different variants in SOX10 gene (two nonsense and one frameshift n).

PMID:29681101 reported the identification of a novel frameshift SOX10 variant in a female infant with PCWH disease.

PMID:32150337 reported a 12-year-old boy with a novel de novo SOX10 frameshift variant and with a combination of clinical presentations including primary peripheral demyelinating neuropathy, hearing loss and visual impairment but absence of Hirschsprung disease and the typical pigmentary changes of hair or skin.

This gene has been associated with relevant phenotypes in both OMIM (MIM #609136) and Gene2Phenotype (with 'definitive' rating on DD, Eye and Skin panels).

Created: 5 Nov 2024, 6:38 p.m. | Last Modified: 5 Nov 2024, 6:38 p.m.

Panel Version: 6.108

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
PCWH syndrome, OMIM:609136

Publications

• 15004559
• 29681101
• 32150337

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - syndrome with non-neurological features / Broader phenotype: PERIPHERAL DEMYELINATING NEUROPATHY, CENTRAL DYSMYELINATION, WAARDENBURG SYNDROME, AND HIRSCHSPRUNG DISEASE; PCWH (Shah-Waardenburg syndrome, neurologic variant)

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 uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.

Created: 11 Jun 2019, 1:40 p.m.

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.

I don't know

2 patients tested in Bristol with frameshift variants and phenotype specifically described PCWH (peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease) - no family testing. Not pure neuropathy gene but this does appear to be a feature. PMID: 21898658 - several cases with PCWH

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

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
PCWH syndrome, 609136; Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584; Waardenburg syndrome, type 4C, 613266

Publications

• 21898658

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

I don't know

Green List (high evidence)

now that r78 inclues complex phenotpyes should presumably be included

Created: 20 Oct 2024, 10:48 a.m. | Last Modified: 20 Oct 2024, 10:48 a.m.

Panel Version: 5.19

Complex phenotype

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease.

Publications

• 32150337: 29681101: 28328136

Complex phenotype

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