Limb disordersGene: SUFU
De Mori AJHG 101:552-63;2017
Created: 1 Aug 2019, 5:10 p.m. | Last Modified: 1 Aug 2019, 5:10 p.m.
Panel Version: 1.24
Comment on list classification: 3 out of 4 children from 2 families had post-axial polydactyly so rating amber. Rating agreed with Genomics England clinical team.
Created: 26 Nov 2019, 12:17 a.m. | Last Modified: 26 Nov 2019, 12:17 a.m.
Panel Version: 1.122
Associated with Joubert syndrome 32 (#617757) in OMIM and Joubert Syndrome with Cranio-facial and Skeletal Defects in Gene2Phenotype (probable).
PMID: 28965847 - Mori et al 2017 - 2 cases. They report four children from two unrelated consanguineous families (from Italy and Egypt) carrying homozygous missense variants (c.1217T>C,p.Ile406Thr and c.1218C>G,p.Ile406Met) in SUFU. The children presented with congenital ataxia and cerebellar vermis hypoplasia with elongated superior cerebellar peduncles (mild "molar tooth sign"), typical cranio-facial dysmorphisms (hypertelorism, depressed nasal bridge, frontal bossing), and 3 had postaxial polydactyly.
In family 1, the two affected siblings also had a homozygous missense variant in CDHR1 but is expressed only in the outer nuclear layer of the retina and pathogenic variants of this gene are known to cause an autosomal-recessive form of cone-rod dystrophy with onset in the late second decade of life (older than the probands).
Functional studies on fibroblasts and cell lines showed that the mutant proteins were less stable and more rapidly degraded than SUFU WT and had impaired ability to bind GLI3 and promote its cleavage into the repressor form GLI3R, while they maintained unaltered ability to bind GLI1. These findings suggest that both variants are hypomorphic alleles, resulting only in a partial loss of the normal gene function.
Created: 7 Aug 2019, 10:16 a.m. | Last Modified: 7 Aug 2019, 10:16 a.m.
Panel Version: 1.39
Gene suggested for the panel by Andrew Wilkie, Oxford University Hospitals NHS Foundation Trust
Sources: Expert list
Created: 1 Aug 2019, 4:24 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Gene: sufu has been classified as Amber List (Moderate Evidence).
Publications for gene: SUFU were set to
Phenotypes for gene: SUFU were changed from Joubert syndrome 32, 617757); Joubert Syndrome with Cranio-facial and Skeletal Defects to Joubert syndrome 32, 617757; Joubert Syndrome with Cranio-facial and Skeletal Defects
Phenotypes for gene: SUFU were changed from to Joubert syndrome 32, 617757); Joubert Syndrome with Cranio-facial and Skeletal Defects
gene: SUFU was added gene: SUFU was added to Limb disorders. Sources: Expert list Mode of inheritance for gene: SUFU was set to BIALLELIC, autosomal or pseudoautosomal Review for gene: SUFU was set to AMBER