Severe microcephalyGene: SMC1A
As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62
Comment on list classification: Updated rating from Red to Green: SMC1A is part of the Cornelia de Lange phenotypic series. >3 cases of SMC1A variants causing CdLS, although microcephalic component is rarer than in other forms of CdLS.
Created: 2 Mar 2017, 3:49 p.m.
Added gene duplication based on PMID:27164022 who report a CdLS patient with duplication of the gene SMC1A (2nd case of a duplication of the gene SMC1A).
Created: 2 Mar 2017, 3:11 p.m.
Although the Cornelia de Lange syndromes (CdLS) are not part of the primary dwarfism spectrum and typically present with additional features other than microcephaly, they are included in this panel after clinical discussion, since a small proportion of cases may overlap with the microcephaly primary dwarfism spectrum.
Created: 2 Mar 2017, 3:07 p.m.
Comment on mode of inheritance: MOI confirmed by OMIM.
Created: 2 Mar 2017, 12:44 p.m.
Phenotypes for gene: SMC1A were changed from Cornelia de Lange syndrome 2, 300590 (includes microcephaly) to Cornelia de Lange syndrome 2, OMIM:300590; Cornelia de Lange syndrome 2, MONDO:0010370; Developmental and epileptic encephalopathy 85, with or without midline brain defects, OMIM:301044; Developmental and epileptic encephalopathy, 85, with or without midline brain defects, MONDO:0026771
Source NHS GMS was added to SMC1A.
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.
This gene has been classified as Green List (High Evidence).
Mode of inheritance for SMC1A was changed to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
SMC1A was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Literature
SMC1A was created by rfoulger