Early onset or syndromic epilepsy

Gene: FZR1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:59 p.m. | Last Modified: 24 Feb 2025, 5:59 p.m.

Panel Version: 7.39

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (four unrelated cases) for the promotion of this gene to green rating in the next GMS update.

Created: 19 Jul 2024, 4:33 p.m. | Last Modified: 19 Jul 2024, 4:33 p.m.

Panel Version: 5.28

PMID:31318984 reported the identification of a novel heterozygous missense FZR1 variant (c.560A>G/ p.Asp187Gly) in a 4-year-old boy, born from non-consanguineous Spanish parents, who presents with severe antenatal microcephaly, global developmental delay, and refractory epilepsy. There is some functional evidence available for this variant.

PMID:34788397 reported the identification of three de novo missense FZR1 variants (c.559G>A/ p.Asp187Asn, c.999C>G/ p.Asn333Lys & c.999C>A/ p.Asn333Lys) in three unrelated individuals from different descents (Turkish, Moroccan and Afghan) presenting with childhood-onset generalized epilepsy, intellectual disability, and mild ataxia. There is functional evidence available for variants reported in this study.

This gene has been associated with relevant phenotypes in OMIM (MIM #620145) and Gene2Phenotype (with 'strong' rating on the DD panel).
Sources: Literature

Created: 19 Jul 2024, 4:29 p.m. | Last Modified: 19 Jul 2024, 4:31 p.m.

Panel Version: 5.27

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental and epileptic encephalopathy 109, OMIM:620145

Publications

• 31318984
• 34788397