Ciliopathies
Gene: SUFU
Heterozygous truncating variants in SUFU in 15 subjects from 6 unrelated families of various ethnic backgrounds (familial and de novo cases). Clinical features of early-onset (congenital) ocular ataxia and developmental delay, with some phenotypic variability. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign of Joubert syndrome. Paper reports that condition reported here and SUFU-associated Basal cell nevus syndrome (Gorlin) are likely allelic disorders, as there is currently no convincing evidence for a clinical overlap.
Functional studies showed no differences in cilia occurrence, morphology, or localization of ciliary proteins, such as smoothened. However, analysis of expression of HH signaling target genes detected a significant increase in the general signaling activity in COMA patient–derived fibroblasts compared with control cells. We observed higher basal HH signaling activity resulting in increased basal expression levels of GLI1, GLI2, GLI3, and Patched1. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign. Knockout mice with SuFu deficiency demonstrated that SuFu is required for proper midhindbrain patterning and controls cerebellar patterning.Created: 8 Feb 2021, 1:53 a.m. | Last Modified: 8 Feb 2021, 1:53 a.m.
Panel Version: 0.92
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
congenital ocular motor apraxia (forme fruste of Joubert syndrome)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Further 22 individuals reported with LoF variants in SUFU and a phenotype described as being on the mild end of JS. Clinical features included congenital oculomotor apraxia, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles.Created: 9 Mar 2022, 2:48 a.m. | Last Modified: 9 Mar 2022, 2:48 a.m.
Panel Version: 1.23
Two unrelated families described with what are postulated to be hypomorphic bi-allelic variants in this gene and Joubert syndrome. Note gene also causes dominant Basal Cell Nevus Syndrome.Created: 29 Feb 2020, 6:14 a.m. | Last Modified: 29 Feb 2020, 6:14 a.m.
Panel Version: 0.68
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Joubert syndrome 32, MIM#617757; SUFU-related neurodevelopmental disorder, Joubert-like
Publications
Phenotypes for gene: SUFU were changed from Joubert syndrome 32, MIM#617757 to Joubert syndrome 32, MIM#617757; SUFU-related neurodevelopmental disorder, Joubert-like
Publications for gene: SUFU were set to 28965847
Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: sufu has been classified as Green List (High Evidence).
Gene: sufu has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SUFU were changed from to Joubert syndrome 32, MIM#617757
Publications for gene: SUFU were set to
Mode of inheritance for gene: SUFU was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Gene: sufu has been classified as Amber List (Moderate Evidence).
gene: SUFU was added gene: SUFU was added to Ciliopathies_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: SUFU was set to Unknown