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Childhood onset hereditary spastic paraplegia v8.17 FICD Arina Puzriakova Tag recurrent-variant tag was added to gene: FICD.
Childhood onset hereditary spastic paraplegia v8.17 FICD Arina Puzriakova Publications for gene: FICD were set to 36136088
Childhood onset hereditary spastic paraplegia v8.16 FICD Arina Puzriakova edited their review of gene: FICD: Added comment: This gene was reassessed in light of the amber review by John Taylor, highlighting that two distinct phenotypes linked to similar variants located in the catalytic motif of FICD have been assessed differently.

FICD was rated amber on Neonatal diabetes (293) in context of infantile diabetes and neurodevelopmental delay associated with a single variant p.Arg371Ser, in three consanguineous families, two of which shared a common haplotype (PMID: 36704923).

A separate association with severe motor neuron disease (rated green on this panel) is based on four unrelated families from different ethnic backgrounds, who all harbour the p.Arg374His variant, which was homozygous in all but one case where the variant was present in a compound heterozygous state with a frameshift variant, p.Gly370GlufsTer53. One patient from this cohort also had diabetes mellitus. Haplotype analysis did indicate that there is a shared haplotype in all patients with the p.Arg374His variant, strongly suggesting a founder effect (PMID: 36136088).

Recently, an additional four individuals from two families were reported (PMID: 40062579) with variants affecting the Arg374 residue, who presented with complicated HSP and diabetes mellitus, merging these two previously distinct presentations.
The report describes one Serbian family, comprising 2 sibs with cHSP (age of onset: 5 and 6) and diabetes mellitus (age of diagnosis: 25 and 27). The sibs had the recurrent homozygous variant p.Arg374His - however, the haplotype identified in the previous report was not found in this family, suggesting that this is an independent event.
The second was a consanguineous family from Saudi Arabia with 2 sibs affected by progressive HSP and diabetes (one prediabetic) - age of onset unclear but paediatric. This family harboured a novel homozygous variant, p.Arg374Cys. No cognitive deficits were reported in either family.

The coexistence of motor neuron disease and diabetes suggests a broader range of neurological and metabolic effects of FICD dysfunction which does warrant further investigation. It is possible that these presentations may be more related than initially thought - individuals diagnosed with infancy-onset diabetes mellitus may develop spasticity later in life, and vice versa.

Overall the recent report does lend additional support for inclusion of FICD on this panel. This gene will also be added to the Monogenic diabetes (472) panel to cover the diabetes phenotype with later onset than the initial report which was reviewed on the Neonatal diabetes (293) panel.; Changed publications to: 36704923, 36136088, 40062579; Changed phenotypes to: Spastic paraplegia 92, autosomal recessive, OMIM:620911
Childhood onset hereditary spastic paraplegia v8.10 FICD John Taylor reviewed gene: FICD: Rating: AMBER; Mode of pathogenicity: None; Publications: 36136088, 36704923; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.6 FICD Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FICD.
Childhood onset hereditary spastic paraplegia v7.6 FICD Arina Puzriakova Tag Q3_24_promote_green was removed from gene: FICD.
Childhood onset hereditary spastic paraplegia v7.6 FICD Arina Puzriakova reviewed gene: FICD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.5 FICD Arina Puzriakova Source Expert Review Green was added to FICD.
Source NHS GMS was added to FICD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v6.9 FICD Achchuthan Shanmugasundram Classified gene: FICD as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v6.9 FICD Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated families and functional work) for the association of this gene with green rating on the next GMS update.
Childhood onset hereditary spastic paraplegia v6.9 FICD Achchuthan Shanmugasundram Gene: ficd has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v6.8 FICD Achchuthan Shanmugasundram gene: FICD was added
gene: FICD was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Q3_24_promote_green tags were added to gene: FICD.
Mode of inheritance for gene: FICD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FICD were set to 36136088
Phenotypes for gene: FICD were set to Spastic paraplegia 92, autosomal recessive, OMIM:620911
Review for gene: FICD was set to GREEN
Added comment: 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.

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