Hereditary neuropathy or pain disorder

Gene: FICD

Green List (high evidence)

The rating of this gene has been updated to green 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
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (three unrelated families with the same homozygous variant and functional studies) for the association of this gene with green rating in the next GMS update.

Created: 23 Oct 2024, 4 p.m. | Last Modified: 23 Oct 2024, 4 p.m.

Panel Version: 5.71

PMID:36136088 reported three unrelated families with recurrent homozygous missense variant in FICD gene (p.Arg374His) and the patients presented with a a neurodegenerative disease of upper and lower motor neurons. A patient from one further family was identified with compound heterozygous variants in FICD gene (p.Arg374His and p.Gly370GlufsTer53).

All these patients had onset of symptoms in childhood with progressive course. Their clinical manifestations included severe lower limb spasticity and mild upper limb spasticity. In addition, nerve conduction test showed motor neuropathy in the four patients with homozygous p.Arg374His variant, whereas this test was not done in the patient with compound heterozygous variants.

Fibroblasts from patients with FICD variants have abnormally increased levels of AMPylated and thus inactivated BiP.

This gene has been associated with relevant phenotypes in OMIM (MIM #620911).
Sources: Literature

Created: 23 Oct 2024, 3:58 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 92, autosomal recessive, OMIM:620911

Publications

• 36136088