Early onset or syndromic epilepsy

Gene: AGMO

Comment on list classification: Gene was added to the panel and rated Amber by Zornitza Stark. Only 1 of the 3 individuals from PMIDs:31555905 and 27000257 is reported with epilepsy. Therefore rated Red awaiting further evidence.

Created: 1 Jun 2020, 4:44 p.m. | Last Modified: 1 Jun 2020, 4:44 p.m.

Panel Version: 2.82

PMID:27000257 (2016) Alrayes et al., 2016 enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability. They identified a novel homozygous deletion mutation (c.967delA; p.Glu324Lysfs12*) in exon 10 of the alkylglycerol monooxygenase (AGMO) gene in 2 brothers. Population screening of 178 ethnically matched control chromosomes and consultation of the ExAC database confirmed that this variant was not present outside the family. Epilepsy is not mentioned amongst their phenotypes.

Created: 1 Jun 2020, 4:31 p.m. | Last Modified: 1 Jun 2020, 4:46 p.m.

Panel Version: 2.82

PMID:31555905. Okur et al., report rare nonsense in-frame deletion and missense compound heterozygous variants in AGMO in 2 unrelated individuals- an 8 year old European girl, and 4-year old Ashkenazi Jewish boy. The girl harboured variants p.Trp130Ter & p.Gly238Cys. The boy harboured variants p.Gly144Arg and p.Tyr236del. Note that there is one individual in gnomAD who is homozygous for the p.Gly144Arg variant. Table 1 also mentions 'MTHFR C677T homozygous' for the boy, but this is not referred to within the text. The authors demonstrated significantly diminished enzyme activity for all disease-associated variants. Seizures were reported for the girl with generalized tonic-clonic seizures beginning age 2 months (and controlled with medication). Seizures were not reported for the boy, though he has a nephew with epilepsy.

Created: 1 Jun 2020, 4:28 p.m. | Last Modified: 1 Jun 2020, 4:42 p.m.

Panel Version: 2.81

I don't know

Three unrelated families reported, though epilepsy not an invariable feature.
Sources: Expert list

Created: 21 Jan 2020, 6:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
microcephaly; intellectual disability; epilepsy

Publications

• 31555905
• 27000257