Skeletal ciliopathies

Gene: SUFU

Amber List (moderate evidence)

SUFU (SUFU negative regulator of hedgehog signaling)
EnsemblGeneIds (GRCh38): ENSG00000107882
EnsemblGeneIds (GRCh37): ENSG00000107882
OMIM: 607035, Gene2Phenotype
SUFU is in 18 panels

4 reviews

Eleanor Williams (Genomics England Curator)

PMID:28965847 - De Mori et al 2017 - 4 subjects from 2 families. All subjects presented peculiar facial dysmorphisms (hypertelorism, broad and depressed nasal bridge, frontal bossing), oculomotor apraxia, developmental delay with mild intellectual impairment, gait ataxia, and dysarthria. Three of them had post-axial polydactyly and two had global macrosomia with macrocephaly. One child also showed a few small dyskeratotic pits on the foot soles
Created: 11 Jul 2019, 3:11 p.m. | Last Modified: 27 Nov 2019, 3:12 p.m.
Panel Version: 0.21

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Amber. Probable DD-G2P gene for Joubert Syndrome. 2 unrelated families from 1 paper. Biochemical assays in the paper (PMID:28965847) show that SUFU missense variants impair GLI3 binding, but further cases and/or animal model required for diagnostic rating.
Created: 1 Nov 2018, 2:34 p.m.
Added 'watchlist' tag.
Created: 16 Oct 2018, 8:28 p.m.
As the Reviewers state, PMID:28965847 (De Mori et al., 2017) performed whole-exome sequencing in subjects with Joubert syndrome and identified 4 children from 2 unrelated families (Italian and Egyptian) carrying homozygous missense variants in SUFU; c.1217T-C, NM_016169.3, p.I406T in the Italians, and c.527A-G, NM_016169.3, p.H176R in the Egyptians. The Italian patients also carried a homozygous T716S mutation in the CDHR1 gene. Three of the children had postaxial polydactyly.
Created: 16 Oct 2018, 8:20 p.m.

Andrea Nemeth (University of Oxford)

Green List (high evidence)

Four mutations in two consanguineous families, causing a complex Joubert-like phenotype with dysmorphic features and a molar tooth sign. Extensive laboratory evidence also provided on the role of this gene in cilial function. The paper (28965847) is from two of the largest groups in the Joubert syndrome/ciliopathy field, so although it is only one publication I think it just makes it into the green list, but with review recommended.
Created: 16 Sep 2018, 7:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Zornitza Stark (Australian Genomics)

I don't know

4 individuals from two unrelated families reported in the literature with hypomorphic bi-allelic variants in this gene and a Joubert syndrome phenotype. Probably merits Amber.
Created: 7 Aug 2018, 4:53 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert Syndrome 32, MIM#617757

Publications

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

History Filter Activity

11 Jul 2019, Gel status: 2

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

Eleanor Williams (Genomics England Curator)

gene: SUFU was added gene: SUFU was added to Skeletal ciliopathies. Sources: Expert list,Expert Review Amber Mode of inheritance for gene: SUFU was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SUFU were set to 28965847 Phenotypes for gene: SUFU were set to Joubert syndrome 32, 617757