Early onset or syndromic epilepsy

Gene: GFM1

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.

Created: 25 Nov 2019, 8:51 p.m. | Last Modified: 25 Nov 2019, 8:51 p.m.

Panel Version: 1.442

PMID:28216230 (Simon et al., 2017) report 2 brothers with compound het variants in GFM1 (maternally-inherited p.Arg250Trp and paternally-inherited p.Gly230_231Glnins19). The younger brother (P1) developed seizures by 4.5 months, characterised as infantile spasms. He has remained seizure free on treatment with topiramate. No seizures were noted for the brother who died age 10 months from multiple organ failure. The authors suggest additional modifier genes may be responsible for the different in severity between the brothers.

Created: 21 Nov 2019, 1:27 p.m. | Last Modified: 21 Nov 2019, 1:27 p.m.

Panel Version: 1.411

PMID:26937387 (Ravn et al., 2015) describe 3 patients with novel GFM1 variants. Patient 3 (a girl of non-consanguineous parents) had epileptic seizures beginning at 2 months old. She died at 3 months during a febrile episode.

Created: 21 Nov 2019, 1:27 p.m. | Last Modified: 21 Nov 2019, 1:27 p.m.

Panel Version: 1.411

PMID:21986555. Galmiche et al., 2012 report two unrelated patients with homozygous GFM1 variants (R671C). The parents were both heterozygous for this variant For the first patient (an Algerian boy from consanguineous parents), no clinical seizures were noted but EEG showed burst of multifocal spikes.

Created: 21 Nov 2019, 1:26 p.m. | Last Modified: 21 Nov 2019, 1:26 p.m.

Panel Version: 1.411

PMID:25852744. Brito et al., 2015 report an infant born to unrelated Caucasian parents with seizures amongst her phenotype (starting age 7 months) and compound het variants in GFM1 (Gly469Valfs*84 and Arg671Cys). The authors summarise clinical features of previous GFM1-deficient patients and note seizures in 5/12 patients.

Created: 21 Nov 2019, 1:26 p.m. | Last Modified: 21 Nov 2019, 1:26 p.m.

Panel Version: 1.411

PMID:21119709. In a girl, born of consanguineous parents, with combined oxidative phosphorylation deficiency, Smits et al. (2011) identified a homozygous R250W variant in GFM1. The patient had refractory seizures amongst her phenotypes. This paper is referred to in the review by Tracy Lester.

Created: 21 Nov 2019, 1:26 p.m. | Last Modified: 21 Nov 2019, 1:26 p.m.

Panel Version: 1.411

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: 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

insufficient information to assign to the Green List (only one case report)

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
Combined oxidative phosphorylation deficiency, 609060

Publications

• 21119709

Seizures are part of the phenotype.

Created: 14 Aug 2018, 9:45 a.m.

Phenotypes
Combined oxidative phosphorylation deficiency 1, MIM#609060

Publications

• 25852744, 26937387, 28216230, 23430926, 21986555

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