Fetal anomalies
Gene: SMO

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

2 reviews

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

Created: 24 Aug 2020, 3:46 a.m.

Panel version: Imported from Polymicrogyria and Schizencephaly panel version 0.92

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Bi-allelic loss-of-function variations in SMO reported in seven individuals from five independent families. Wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis).
Somatic recurrent missense variant, L412F causes Curry-Jones syndrome.
Created: 28 Feb 2022, 7:52 a.m. | Last Modified: 28 Feb 2022, 7:52 a.m.

Panel Version: 0.4355

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Microcephaly; congenital heart disease; polydactyly; aganglionosis, Pallister-Hall-like syndrome, MIM# 241800

Publications

Created: 24 Dec 2019, 12:17 a.m.

Panel version: 0.4355

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Expert Review Green
Genomics England PanelApp
Expert list

Phenotypes

Curry-Jones syndrome, somatic mosaic, MIM#601707

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