Intellectual disability
Gene: SUFU

SUFU (SUFU negative regulator of hedgehog signaling)
EnsemblGeneIds (GRCh38): ENSG00000107882
EnsemblGeneIds (GRCh37): ENSG00000107882
OMIM: 607035, Gene2Phenotype
SUFU is in 21 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

After NHS Genomic Medicine Service consideration, the rating of this gene has been updated to Green but the mode of inheritance has been set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal. Additional comments from reviewing GLHs: 'Consensus view: Monoallelic and biallelic'.
Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.

Panel Version: 5.286

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update under a MONOALLELIC inheritance pattern only, unless the NHS GMS working group disagree and feel the MOI should include both mono- and biallelic variants based on the current evidence.
Created: 12 Dec 2022, 12:48 p.m. | Last Modified: 12 Dec 2022, 12:48 p.m.

Panel Version: 4.9

Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical team) it was decided that based on the current evidence the MOI should be set to 'monoallelic' only for now but with a 'watchlist' tag to monitor for additional biallelic cases relating to a Joubert-like presentation.
Created: 12 Dec 2022, 12:44 p.m. | Last Modified: 12 Dec 2022, 12:44 p.m.

Panel Version: 4.7

To date, only 2 unrelated cases with a Joubert-like phenotype and hypomorphic biallelic variants have been reported (PMID: 28965847). The phenotype is listed in OMIM and G2P (strong confidence category). There is also a knockout mouse model displaying severely abnormal cerebellar morphology (PMID: 21289193). However, an Amber classification was previously selected based on the evidence and there have been no further publications of recessive disease since the initial case report.

Recently, two papers (PMID: 33024317, 34675124) were published describing 23 total families with heterozygous variants in individuals who presented a milder phenotype within the Joubert clinical spectrum. Phenotype was characterised by congenital ocular motor apraxia (COMA) in all individuals and other variable features such as DD/ID, ataxia, cerebellar and brainstem anomalies. There was a lack of conclusive retinal, kidney, liver or skeletal involvement typical of Joubert syndrome. Some variants were inherited from asymptomatic carrier parents suggesting reduced penetrance. None had evidence of cancer.
Created: 12 Dec 2022, 12:38 p.m. | Last Modified: 12 Dec 2022, 12:38 p.m.

Panel Version: 4.4

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 32, OMIM:617757

Publications

Created: 12 Dec 2022, 12:38 p.m.
Last Modified: 12 Dec 2022, 12:38 p.m.
Panel version: 5.286

Catherine Snow (Genomics England)

Comment on mode of inheritance: From 'Fetal Anomalies@ panel - Changed MOI from 'both biallelic and monoallelic' to biallelic based on comment by Deirdre Cilliers: Joubert syndrome 32 (MIM:617757) has biallelic inheritance, and Basal cell nevus syndrome (MIM:109400) has monoallelic inheritance.
Created: 4 Jun 2019, 3:57 p.m.

Comment on list classification: Gene identified in literature PMID:30914295 as missing in PanelApp compared to other curated gene list for ID genes.

SUFU has four disease phenotypes associated in OMIM in which just one is relevant for ID phenotype - Joubert syndrome 32, 617757.

In 4 children from 2 unrelated consanguineous families (Egyptian and Italian) with Joubert syndrome-32 (JBTS32; 617757), De Mori et al. (2017, PMID:28965847) identified 2 different homozygous missense mutations in the SUFU gene, mild ID reported in both families.

SUFU is Amber on the related 'Rare multisystem ciliopathy disorders' panel (for Joubert syndrome) and Amber on the 'Fetal anomalies' panel. Likewise due to number of cases SUFU will be classed as Amber.
Created: 4 Jun 2019, 3:57 p.m.

Created: 4 Jun 2019, 3:57 p.m.

Panel version: Imported from Intellectual disability update May 2019 panel version 0.146

Details

Mode of Inheritance

BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS
Literature
Literature

Phenotypes

Joubert syndrome 32, OMIM:617757

OMIM

607035

Clinvar variants

Variants in SUFU

Penetrance

Incomplete

Publications

Panels with this gene