Submission Details

Autosomal dominant

09/08/2020

The SUFU gene is located on chromosome 10 at 10q24.32 and encodes the suppressor of fused homolog protein, which is a negative regulator for the hedgehog/smoothened signaling pathway. The SUFU gene was first reported in relation to Gorlin syndrome (known as nevoid basal cell carcinoma syndrome) and atypical Gorlin syndrome, in 2009 (19533801; Pastorino et al. 2009). Evidence supporting this gene-disease relationship includes case-level data and experimental data. From a selection of literature, at least seven variants have been reported in a heterozygous state in eight affected individuals in six publications (19533801: Pastorino et al. 2009; 22829011: Kijima et al. 2012; 25403219: Smith et al. 2014; 29892665: Ogden et al. 2018; 29356994: Huq et al. 2018; 31485359: Askaner et al. 2019). The mechanism for disease is loss of function. Experimental evidence demonstrates that a splice donor variant was unable to interact with GLI transcription factors, resulting in activation of SHH pathway target genes (12068298: Taylor et al. 2002; 16459298: Svard et al. 2006). In a mouse model, in which mice were heterozygous for functional Sufu, a skin phenotype similar to Gorlin syndrome was observed (16459298: Svard et al. 2006). In summary, SUFU is definitively associated with autosomal dominant nevoid basal cell carcinoma syndrome.

19533801 22829011 25403219 29892665 29356994 31485359 12068298 16459298