Severe microcephalyGene: AGMO
Comment on list classification: Upgraded from Red to Amber. With addition of the publication identified by Zornitza Stark, there are now 2/3 unrelated cases with microcephaly (PMIDs: 31555905 and 27000257). Rating Amber awaiting further cases prior to inclusion as diagnostic-grade.
Created: 27 Jan 2021, 10:47 a.m. | Last Modified: 27 Jan 2021, 10:47 a.m.
Panel Version: 2.82
PMID:31555905. Okur et al., report different compound heterozygous variants in AGMO in 2 unrelated individuals (8 year old European girl, and 4-year old Ashkenazi Jewish boy). They demonstrated significantly diminished enzyme activity for all disease-associated variants. 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. Only the girl displayed microcephaly (Table 1).
Created: 27 Jan 2021, 10:42 a.m. | Last Modified: 27 Jan 2021, 10:42 a.m.
Panel Version: 2.80
Two more unrelated families reported.
Created: 30 Aug 2020, 5:30 a.m. | Last Modified: 30 Aug 2020, 5:30 a.m.
Panel Version: 2.19
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
microcephaly; intellectual disability; epilepsy
Variants in this GENE are reported as part of current diagnostic practice
As discussed with the GMS Neurology Specialist Test Group webex call 11thJuly 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62
PMID:27000257 (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. Population screening of 178 ethnically matched control chromosomes and consultation of the Exome Aggregation Consortium database confirmed that this mutation was not present outside the family.
Created: 27 Feb 2017, 11:43 a.m.
Gene: agmo has been classified as Amber List (Moderate Evidence).
Publications for gene: AGMO were set to 27000257
Source NHS GMS was added to AGMO.
2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.
AGMO was created by rfoulger
AGMO was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Literature