Adult onset neurodegenerative disorder

Gene: C19orf12

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 12:22 p.m. | Last Modified: 1 Feb 2023, 12:22 p.m.

Panel Version: 3.49

Monfrini et al (PMID: 29295770) and Gregory et al (PMID: 31087512) have reported heterozygous pathogenic C19ORF12 variants in patients with neurodegeneration with brain iron accumulation 4 (OMIM: 614298). Therefore, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.

Created: 7 Apr 2022, 12:29 p.m. | Last Modified: 7 Apr 2022, 12:29 p.m.

Panel Version: 2.272

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 29295770
• 31087512

Green List (high evidence)

There is evidence for both mono-allelic and bi-allelic variants causing disease, consider changing MOI.

Created: 25 Sep 2020, 12:36 a.m. | Last Modified: 25 Sep 2020, 12:36 a.m.

Panel Version: 2.16

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Neurodegeneration with brain iron accumulation 4, MIM# 614298

Publications

• 23278385
• 21981780
• 23269600

Red List (low evidence)

Neurodegeneration with brain iron accumulation-4 (NBIA4) is an autosomal recessive neurodegenerative disorder characterized by progressive spastic paraplegia, parkinsonism unresponsive to L-DOPA treatment, and psychiatric or behavioral symptoms. Other neurologic features, including optic atrophy, eye movement abnormalities, dystonia, dysphagia, dysarthria, and motor axonal neuropathy, may occur. >3 cases.

Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.

Panel Version: 1.99

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
mitochondrial membrane protein-associated neurodegeneration; Dystonia; neurodegeneration with brain iron accumulation-4; Neurodegeneration with brain iron accumulation 4

Green List (high evidence)

Late onset reported.

Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.

Panel Version: 1.72

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
mitochondrial membrane protein-associated neurodegeneration; Dystonia; neurodegeneration with brain iron accumulation-4; Neurodegeneration with brain iron accumulation 4

Publications

• 23278385

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

Green List (high evidence)

As discussed with the GMS Neurology Specialist Test Group webex call11th September 2019 : The Specialist Test Group all agreed that there is enough evidence to rate this gene Green

Created: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.

Panel Version: 1.106

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.

Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.

Panel Version: 1.101

Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.

Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.

Created: 23 Apr 2019, 5:35 p.m.

Green List (high evidence)