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Intellectual disability

Gene: FRRS1L

Amber List (moderate evidence)

FRRS1L (ferric chelate reductase 1 like)
EnsemblGeneIds (GRCh38): ENSG00000260230
EnsemblGeneIds (GRCh37): ENSG00000260230
OMIM: 604574, Gene2Phenotype
FRRS1L is in 4 panels

3 reviews

Helen Brittain (Genomics England Curator)

I don't know

I can only see that developmental problems occur after the onset of seizures, therefore this gene may be better addressed via the EIEE route. This is green on the genetic epilepsy syndromes panel already. This decision can be reviewed in light of the scope of the ID panel, as needed.
Created: 19 Jul 2019, 11:44 a.m. | Last Modified: 19 Jul 2019, 11:44 a.m.
Panel Version: 0.203

Catherine Snow (Genomics England)

Comment on list classification: FRRS1L identified in literature PMID:30914295 as missing in PanelApp compared to other curated gene list for ID genes.

FRRS1L was added to the ID panel and rated Green by Konstantinos Varvagiannis. Several individuals homozygous for LoF variants have been reported by Madeo et al. (PMID:27236917) and Shaheen et al. (PMID:27239025 - 2 individuals of this family previously published in 21147040). Phenotype is relevant for inclusion in ID panel and FRRS1L is probable in Gene2Phenotype although no phenotypes have been assigned to the G2P entry.
Created: 20 May 2019, 4:14 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Biallelic pathogenic variants in FRRS1L cause Epileptic encephalopathy, early infantile, 37 (EIEE37 - MIM 616981).

Several individuals homozygous for LoF variants have been reported by Madeo et al. (PMID:27236917) and Shaheen et al. (PMID:27239025 - 2 individuals of this family previously published in 21147040). DD and choreoathetotic movement disorder may precede onset of seizures and subsequent regression. Intellectual disability was a universal feature.

Both articles and the respective phenotype are summarized in OMIM.

Extensive functional studies have been performed in the article by Madeo et al. as well as in PMID: 29276473 (Han et al.) and suggest a role in glutamatergic transmission.

FRRS1L is included in the DD panel of G2P, associated with Epileptic encephalopathy with continuous spike-and-wave during sleep.

This gene is included in gene panels for ID offered by several diagnostic laboratories (incl. Radboudumc).

As a result, this gene can be considered for inclusion in the ID panel as green, if the phenotype of EIEE is thought to be relevant.
Sources: Literature, Radboud University Medical Center, Nijmegen
Created: 19 Dec 2018, 12:45 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 37 (MIM 616981)

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Epileptic encephalopathy, early infantile, 37 (MIM 616981)
  • Epileptic encephalopathy, early infantile, 37, 616981
OMIM
604574
Clinvar variants
Variants in FRRS1L
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

25 Jul 2019, Gel status: 2

Added New Source, Set Phenotypes, Set publications, Status Update

Catherine Snow (Genomics England)

Source Expert Review Amber was added to FRRS1L. Added phenotypes Epileptic encephalopathy, early infantile, 37, 616981 for gene: FRRS1L Publications for gene FRRS1L were changed from 27236917; 27239025; 21147040; 29276473 to 29276473; 27239025; 21147040; 27236917; 30914295 Rating Changed from No List (delete) to Amber List (moderate evidence)

19 Dec 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: FRRS1L was added gene: FRRS1L was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: FRRS1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FRRS1L were set to 27236917; 27239025; 21147040; 29276473 Phenotypes for gene: FRRS1L were set to Epileptic encephalopathy, early infantile, 37 (MIM 616981) Penetrance for gene: FRRS1L were set to Complete Review for gene: FRRS1L was set to GREEN gene: FRRS1L was marked as current diagnostic