Polymicrogyria and Schizencephaly

Gene: SMO

Amber List (moderate evidence)

SMO (smoothened, frizzled class receptor)
EnsemblGeneIds (GRCh38): ENSG00000128602
EnsemblGeneIds (GRCh37): ENSG00000128602
OMIM: 601500, Gene2Phenotype
SMO is in 13 panels

1 review

Paul De Fazio (Victorian Clinical Genetics Services)

I don't know

PMID 27236920 summarises the clinical and molecular findings in 8 unrelated individuals (including individuals reported previously). All 8 had the same somatic mosaic missense variant c.1234C>T p.(Leu412Phe) (absent from gnomAD). 2 had polymicrogyria. Other brain abnormalities reported include agenesis of the corpus callosum, hemimegalencephaly, ventriculomegaly. 1 individual was reported to have a normal brain.

In mouse embryonic fibroblasts, this variant results in constitutive activation (PMID: 24859340).

Other, biallelic germline variants in this gene are associated with Pallister-Hall-like syndrome (MIM#241800) but the MRI findings in individuals with this syndrome don't appear to be applicable to this panel.
Sources: Literature
Created: 24 Aug 2020, 3:46 a.m.

Mode of inheritance
Unknown

Phenotypes
Curry-Jones syndrome, somatic mosaic MIM#601707

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

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

Details

Mode of Inheritance
Unknown
Sources
  • Expert Review Amber
Phenotypes
  • Curry-Jones syndrome, somatic mosaic MIM#601707
Tags
somatic
OMIM
601500
Clinvar variants
Variants in SMO
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

24 Aug 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: smo has been classified as Amber List (Moderate Evidence).

24 Aug 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: smo has been classified as Amber List (Moderate Evidence).

24 Aug 2020, Gel status: 0

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag somatic tag was added to gene: SMO.

24 Aug 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity

Paul De Fazio (Victorian Clinical Genetics Services)

gene: SMO was added gene: SMO was added to Polymicrogyria and Schizencephaly. Sources: Literature Mode of inheritance for gene: SMO was set to Unknown Publications for gene: SMO were set to 27236920; 24859340 Phenotypes for gene: SMO were set to Curry-Jones syndrome, somatic mosaic MIM#601707 Mode of pathogenicity for gene: SMO was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: SMO was set to AMBER gene: SMO was marked as current diagnostic