Limb disordersGene: SMO
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).
This is a distinct condition from Curry-Jones syndrome, which is caused by a recurrent somatic missense variant.
Created: 4 Jun 2020, 11:20 p.m. | Last Modified: 4 Jun 2020, 11:20 p.m.
Panel Version: 2.5
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Microcephaly, congenital heart disease, polydactyly, aganglionosis
Comment on mode of inheritance: Changed MOI from 'Other' in order to capture variants within this gene in our current tiering pipeline.
Created: 5 Nov 2018, 9:05 a.m.
Comment on list classification: Updated rating from Red to Green: sufficient unrelated cases of syndactyly and/or preaxial polydactyly in Curry-Jones patients for inclusion on panel.
Created: 16 Oct 2018, 2:08 p.m.
Comment on mode of inheritance: Somatic mosaic.
Created: 16 Oct 2018, 2:07 p.m.
Added 'somatic' tag.
Created: 16 Oct 2018, 2:06 p.m.
PMID:27236920 (Twigg et al, 2016) analysed 10 unrelated patients with Curry-Jones syndrome including 6 previously reported patients. They identified somatic mosaicism for the identical L412F variant in SMO in 8 of the patients. The patients all showed cutaneous syndactyly and/or preaxial polydactyly.
Created: 2 Oct 2018, 2:23 p.m.
Comment on mode of pathogenicity: Somatic mosaicism.
Created: 2 Oct 2018, 2:21 p.m.
Added 'mosaicism' tag based on PMID:27236920, DD-G2P and OMIM information.
Created: 2 Oct 2018, 2:20 p.m.
Rebecca Foulger: Added 'mosaicism' tag based on
Mode of inheritance for gene: SMO was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: smo has been classified as Green List (High Evidence).
Mode of inheritance for gene: SMO was changed from to Other
Tag somatic tag was added to gene: SMO.
Phenotypes for gene: SMO were changed from Polydactyly to Polydactyly; Curry-Jones syndrome, somatic mosaic, MIM:601500; Cutaneous syndactyly; Preaxial polydactyly
Publications for gene: SMO were set to
Mode of pathogenicity for gene: SMO was changed from None to Other
Tag mosaicism tag was added to gene: SMO.
SMO was added to Limb disorders panel. Sources: Victorian Clinical Genetics Services
SMO was created by Ellen McDonagh