Polymicrogyria and Schizencephaly
Gene: SMO
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: LiteratureCreated: 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
Gene: smo has been classified as Amber List (Moderate Evidence).
Gene: smo has been classified as Amber List (Moderate Evidence).
Tag somatic tag was added to gene: SMO.
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