Hereditary neuropathy or pain disorder

Gene: XK

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)

At least eight XK variants have been associated with OMIM:300842 in numerous cases, including one woman with marked skewing of X inactivation (PMID:8619554) and female members of a family, where the semidominant effect of the variant was suggested by erythrocyte and blood group mosaicism in these cases (PMID:11261514). 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
McLeod syndrome, OMIM:300842

Publications

• 8619554
• 11261514

Green List (high evidence)

Several publications including those given above regarding this well characterised link between XK gene and McLeod syndrome in many patients. Phenotype is acanthosis, haemolysis and elevated CK. Neurological phenotype (from OMIM) "Onset of neurologic symptoms ranges between 25 and 60 years (mean onset 30-40 years), and penetrance appears to be high. Additional symptoms include generalized seizures, neuromuscular symptoms leading to weakness and atrophy, and cardiomyopathy mainly manifesting with atrial fibrillation, malignant arrhythmias, and dilated cardiomyopathy"

Testing not currently offered by UK labs but several accredited European laboratories are offering testing.

Created: 23 Sep 2019, 11:06 a.m. | Last Modified: 23 Sep 2019, 11:06 a.m.

Panel Version: 1.333

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

Phenotypes
McLeod syndrome with or without chronic granulomatous disease OMIM 300842

Publications

• 11761473
• 11761473

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

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: McLeod syndrome, note adult onset

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 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.

Green List (high evidence)

Should be included in R78 as now inlcudes many other complex phenotype genes that can present with neuropathy

Created: 17 Mar 2024, 9:47 p.m. | Last Modified: 17 Mar 2024, 9:47 p.m.

Panel Version: 3.83

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

Phenotypes
Mceod syndrome, Onset 25-60, acanthocytes and Huntington-like syndrome, also epilepsy, cardiomyopathy, axonal motor neuropathy