Early onset or syndromic epilepsy

Gene: UFC1

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

Limited evidence: PMID 29868776 reported 8 patients with a severe neurodevelopmental disorder and of these three had seizures (intractable in two patients).

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with spasticity and poor growth, 618076

Publications

• 27431290

Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 2 variants reported in unrelated cases in which seizures are a phenotypic feature.

Created: 27 Nov 2018, 2:46 p.m.

Green List (high evidence)

Biallelic UFC1 mutations cause Neurodevelopmental disorder with spasticity and poor growth, MIM 618076.

PMID: 29868776 describes 7 individuals (most) born to consanguineous Saudi families (in one case the parents were not consanguineous but originated from the same tribe) as well as a further individual born to distantly related Swiss parents. One of these patients was previously briefly published by the same authors (PMID: 27431290).

The phenotype consisted of developmental delay (8/8 - usually profound), failure to thrive (8/8), short stature and microcephaly (both observed in 7/8), seizures (4/8) and variable brain MRI anomalies in some of these subjects.

Overall, two UFC1 missense variants are reported [NM_016406.3:c.317C>T or p.(Thr106Ile) and c.68G>A or p.(Arg23Gln) the former in the Saudi individuals]. Functional studies demonstrated the hypomorphic nature of the variants.

UFC1 (as well as UFM1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

Epilepsy was a feature in 50% (4/8) of the individuals reported.

As a result this gene can be considered for inclusion in the epilepsy panel as green (or amber).
Sources: Literature, Expert Review

Created: 20 Nov 2018, 10:33 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with spasticity and poor growth, 618076

Publications

• 29868776