Intellectual disability - microarray and sequencing
Gene: SUFU
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
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.
Tag watchlist_moi was removed from gene: SUFU. Tag Q4_22_MOI was removed from gene: SUFU. Tag Q4_22_promote_green was removed from gene: SUFU. Tag Q4_22_expert_review was removed from gene: SUFU.
Source NHS GMS was added to SUFU. Source Expert Review Green was added to SUFU. Mode of inheritance for gene SUFU was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q4_22_expert_review tag was added to gene: SUFU.
Penetrance for gene SUFU was set from to None
Gene: sufu has been classified as Amber List (Moderate Evidence).
Publications for gene: SUFU were set to 21289193; 28965847; 33024317, 34675124
Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SUFU were set to 28965847; 30914295
Phenotypes for gene: SUFU were changed from Joubert syndrome 32, 617757 to Joubert syndrome 32, OMIM:617757
Tag Q4_22_MOI tag was added to gene: SUFU.
Tag watchlist was removed from gene: SUFU. Tag watchlist_moi tag was added to gene: SUFU. Tag Q4_22_promote_green tag was added to gene: SUFU.
Tag watchlist tag was added to gene: SUFU.
Mode of inheritance for gene SUFU was changed from to BIALLELIC, autosomal or pseudoautosomal
gene: SUFU was added gene: SUFU was added to Intellectual disability. Sources: Literature,Expert Review Amber Mode of inheritance for gene: SUFU was set to Publications for gene: SUFU were set to 28965847; 30914295 Phenotypes for gene: SUFU were set to Joubert syndrome 32, 617757